Amount and constitutionReference ranges in CSF

SubstanceLower limitUpper limitUnit

Glucose50[3]80[3]mg/dL

Protein15[3]40[4]45[3]mg/dL

RBCsn/a[3]0[3] / negativecells/L

WBCs0[3]3[3]cells/L

The CSF is produced at a rate of 500 ml/day. Since the brain can contain only 135 to 150 ml, large amounts are drained primarily into the blood through arachnoid granulations in the superior sagittal sinus. Thus the CSF turns over about 3.7 times a day. This continuous flow into the venous system dilutes the concentration of larger, lipoinsoluble molecules penetrating the brain and CSF.[5]The CSF contains approximately 0.3% plasma proteins, or approximately 15 to 40mg/dL, depending on sampling site.[4] CSF pressure ranges from 80 to 100 mmH2O (780980Pa or 4.47.3mmHg) in newborns, and < 200mmH20 (1.94kPa) in normal children and adults, with most variations due to coughing or internal compression of jugular veins in the neck.There are quantitative differences in the distributions of a number of proteins in the CSF. In general, globular proteins and albumin are in lower concentration in ventricular CSF compared to lumbar or cisternal fluid

What is an Amino Acid Sequence?An amino acid sequence, as you might already guessed, is the order in which various amino acids get linked to form a protein or peptide chains. A peptide chain is a long covalently bonded chain of amino acids. If a peptide chain, happens to be a protein, its amino acid sequence alignment is called the 'Primary Structure' of that protein. Branched chain amino acids form all the proteins of the human body.

Proteins and peptide chains are created through the formation of peptide bonds between different amino acids. The amino acid sequence is created through the bonding of the carboxyl group of one amino acid with the amino group of another. This kind of linking goes on until polypeptides are created. To study any protein or for that matter, any molecule in chemistry, one needs to understand its structure first. That is why to study a protein, a biochemist must first find out its amino acid sequence. A protein is much more complex than a peptide chain with hundreds or thousands of amino acids bonding together.

The formation of proteins happens at the cellular level. The recipe or the code for creation of any protein is encoded in the DNA (Deoxyribose Nucleic Acid) molecule. To create every protein, the recipe for creation, must first be deciphered from the DNA molecule and then relayed to the site of protein synthesis. The deciphering part is done in the form of a mRNA (messenger RNA) strand that holds information about creating a protein from a gene. Every amino acid has a specific three letter corresponding code (called a codon) in the DNA sequence. You will have to refer to a codon chart to know the code for every amino acid. In such charts, amino acid abbreviations are generally used.

This mRNA code has a sequence of codons which provides the order of assembling various amino acids together. From the strand of mRNA transported in the cytoplasm, tRNA (transfer RNA) carry the information about the amino acid sequence to a ribosome site for protein assembly. So the order of an amino acid sequence, if known, can be used to decipher the corresponding DNA code segment or gene that created it through reverse engineering!

FUNGSI PROTEIN

Sebagai yang terentang di dalam membrane membentuk jalur atau saluran berisi air yang menembus lipid lapisan ganda sehingga memungkinkan zat-zat larut air yang cukup kecil memasuki saluran, misalnya ion. Setiap saluran dapat terbuka atau tertutup terhadap ion spesifiknya akibat perubahan bentuk saluran sebagai respon terhadap mekanisme pengontrol. Sebagai molekul pembawa yang mengangkut zat-zat yang tidak mampu menembus membrane dengan sendirinya. Dengan demikian saluran dan molekul pembawa keduanya penting dalam transportasi zat-zat antara CES dan CIS. Contoh: Hemoglobin sebagai transport oksigen dalam darah, seruloplasmin sebagai transport tembaga dalam darah. Banyak protein di luar permukaan berfungsi sebagai tempat reseptor yang mengenali dan berikatan dengan molekul-molekul spesifik di lingkungan sekitar sel pengikatan ini mencetus serangkaian kejadian dipermukaan membrane dan di dalam sel yang mengubah aktivitas sel tertentu. Kelompok protein lain berfungsi sebagai enzim yang terikat ke membrane yang mengontrol reaksi-reaksi kimia tertentu dipermukaan dalam atau luar sel. Sel-sel memperlihatkan khususnya pada jenis enzim yang terbenam dalam menbran plasma. Contoh glikolat oksidasi dari glioksisom, dan alkahol dehidrogenase pada fermentasi alcohol. Sebagian protein tersusun dalam sualu jalinan filamentosa dipermukaan bagian dalam membrane dan dihubungkan dengan unsur-unsur protein tertentu pada sitoskleton. Protein lain berfungsi sebagai molekul adhesi sel. Molekul-molekul ini menonjol keluar dari permukaan membrane dan membentuk lengkungan-lengkungan atau anggota badan laju yang digunakan oleh sel untuk saling berpegangan dan untuk melekatkan ke serat-serat jaringan ikat yang menjalin antara sel-sel. Contoh: kolagen jaringan ikat fibrora (kartilago, tulang, tendon), myosin, aktin. Protein lain khususnya bersama dengan karbohidrat penting untuk kemampuan sel mengenali diri dan dalam interaksi sel ke sel. Selain itu protei juga berfungsi sebagai aktivitas hormonal, seperti hormone pertumbuhan yang mengatur pertumbuhan tulang, dan juga pada saat kita digigit ular tubuh akan mengeluarkan enzim hidrolitik (degra dastis). Sebagian protein berfungsi sebagai toksin seperti toksin glistridium botulinun yakni tiksin makanan bacterial letal. Ada juga protein yang berungsi sebagai proteksi seperti antibody yang berinteraksi dengan proein asing, fibrinogen yang digunakan dalam pembekuan darah, juga insulin sebgai regulator metabolism glukosa dalam darah.Dan juga ada sebagian protein yangberfungsi sebagai cadangan dalam tubuh, seperti fertin sebagai cadagan zat besi (limpa) dan juga kasein cadangan asam aminoProteinProteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the genetic code specifies 20 standard amino acids; however, in certain organisms the genetic code can include selenocysteineand in certain archaeapyrrolysine. Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification, which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Proteins can also work together to achieve a particular function, and they often associate to form stable complexes.Of the most distinguishing features of polypeptides is their ability to fold into a globual state, or "structure". The extent to which proteins fold into a defined structure varies widely. Data supports that some protein structures fold into a highly rigid structure with small fluctuations and are therefore considered to be single structure. Other proteins have been shown to undergo large rearrangements from one conformation to another. This conformational change is often associated with a signaling event. Thus, the structure of a protein serves as a medium through which to regulate either the function of a protein or activity of an enzyme. Not all proteins requiring a folding process in order to function as some function in an unfolded state.Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in virtually every process within cells. Many proteins are enzymes that catalyze biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids from food. Through the process of digestion, animals break down ingested protein into free amino acids that are then used in metabolism.SynthesisThe DNA sequence of a gene encodes the amino acid sequence of a protein.Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG (adenine-uracil-guanine) is the code for methionine. Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon.[12] Genes encoded in DNA are first transcribed into pre-messenger RNA (mRNA) by proteins such as RNA polymerase. Most organisms then process the pre-mRNA (also known as a primary transcript) using various forms of post-transcriptional modification to form the mature mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid. In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm, where protein synthesis then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.The process of synthesizing a protein from an mRNA template is known as translation. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain. Proteins are always biosynthesized from N-terminus to C-terminus.The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass, which is normally reported in units of daltons (synonymous with atomic mass units), or the derivative unit kilodalton (kDa). Yeast proteins are on average 466 amino acids long and 53 kDa in mass.[11] The largest known proteins are the titins, a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.Chemical synthesisShort proteins can also be synthesized chemically by a family of methods known as peptide synthesis, which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield.[15] Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology, though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.Structure of proteinsThree possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: Simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).Mostproteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native conformation. Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: Primary structure: the amino acid sequence. Secondary structure: regularly repeating local structures stabilized by hydrogen bonds. The most common examples are the alpha helix, beta sheet and turns. Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule. Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a hydrophobic core, but also through salt bridges, hydrogen bonds, disulfide bonds, and even post-translational modifications. The term "tertiary structure" is often used as synonymous with the term fold. The tertiary structure is what controls the basic function of the protein. Quaternary structure: the structure formed by several protein molecules (polypeptide chains), usually called protein subunits in this context, which function as a single protein complex.Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations", and transitions between them are called conformational changes. Such changes are often induced by the binding of a substrate molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis. In solution proteins also undergo variation in structure through thermal vibration and the collision with other molecules.

Molecular surface of several proteins showing their comparative sizes. From left to right are: immunoglobulin G (IgG, an antibody), hemoglobin, insulin (a hormone), adenylate kinase (an enzyme), and glutamine synthetase (an enzyme).Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen, the major component of connective tissue, or keratin, the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane.A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons.Structure determinationDiscovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function. Common experimental methods of structure determination include X-ray crystallography and NMR spectroscopy, both of which can produce information at atomic resolution. However, NMR experiments are able to provide information from which a subset of distances between pairs of atoms can be estimated, and the final possible conformations for a protein are determined by solving a distance geometry problem. Dual polarisation interferometry is a quantitative analytical method for measuring the overall protein conformation and conformational changes due to interactions or other stimulus. Circular dichroism is another laboratory technique for determining internal beta sheet/ helical composition of proteins. Cryoelectron microscopy is used to produce lower-resolution structural information about very large protein complexes, including assembled viruses;[24] a variant known as electron crystallography can also produce high-resolution information in some cases , especially for two-dimensional crystals of membrane proteins.[25] Solved structures are usually deposited in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.[26]Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X-ray crystallography, one of the major structure determination methods. In particular, globular proteins are comparatively easy to crystallize in preparation for X-ray crystallography. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.[27] Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.Cellular functionsProteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in a particular cell or cell type is known as its proteome.

The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, ATP and glucose.The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (1 M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine.Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Proteinprotein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.[30] Importantly, as interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types.[31][32]EnzymesThe best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process known as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes. The rate acceleration conferred by enzymatic catalysis is often enormous as much as 1017-fold increase in rate over the uncatalyzed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction 3 to 4 residues on average that are directly involved in catalysis.[35] The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.Cell signaling and ligand binding

Ribbon diagram of a mouse antibody against cholera that binds a carbohydrate antigenMany proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.[36]Antibodies are protein components of adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.[38] Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play a role in biological recognition phenomena involving cells and proteins.[39] Receptors and hormones are highly specific binding proteins.Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions.[40]Structural proteinsStructural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton, which allows the cell to maintain its shape and size. Collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells.Other proteins that serve structural functions are motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually. They also generate the forces exerted by contracting muscles.Bovine spongiform encephalopathyClassic image of a cow with BSE. A feature of such disease is the inability of the infected animal to stand.Bovine spongiform encephalopathy (BSE), commonly known as mad-cow disease, is a fatal, neurodegenerative disease in cattle, that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 4 years, usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible. In the United Kingdom, the country worst affected, more than 179,000 cattle have been infected and 4.4 million slaughtered during the eradication program.The disease may be most easily transmitted to human beings by eating food contaminated with the brain or spinal cord of infected carcasses. However, it should also be noted that the infectious agent, although most highly concentrated in nervous tissue, can be found in virtually all tissues throughout the body, including blood. In humans, it is known as new variant CreutzfeldtJakob disease (vCJD or nvCJD), and by October 2009, it had killed 166 people in Britain (the most recent being of a different genotype than other sufferers), and 44 elsewhere with the number expected to rise because of the disease's long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989.A British inquiry into BSE concluded that the epizootic was caused by cattle, who are normally herbivores, being fed the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread. The origin of the disease itself remains unknown. The infectious agent is distinctive for the high temperatures at which it remains viable; this contributed to the spread of the disease in Britain, which had reduced the temperatures used during its rendering process. Another contributory factor was the feeding of infected protein supplements to very young calves.CauseMicroscopic "holes" of tissue sections are examined in the lab. Source: APHISThe infectious agent in BSE is believed to be a specific type of misfolded protein called a prion. Prion proteins carry the disease between individuals and cause deterioration of the brain. BSE is a type of transmissible spongiform encephalopathy (TSE).[12] TSEs can arise in animals that carry an allele which causes previously normal protein molecules to contort by themselves from an alpha helical arrangement to a beta pleated sheet, which is the disease-causing shape for the particular protein. Transmission can occur when healthy animals come in contact with tainted tissues from others with the disease. In the brain these proteins cause native cellular prion protein to deform into the infectious state, which then goes on to deform further prion protein in an exponential cascade. This results in protein aggregates, which then form dense plaque fibers, leading to the microscopic appearance of "holes" in the brain, degeneration of physical and mental abilities, and ultimately death.Different hypotheses exist for the origin of prion proteins in cattle. Two leading hypotheses suggest that it may have jumped species from the disease scrapie in sheep, or that it evolved from a spontaneous form of "mad cow disease" that has been seen occasionally in cattle for many centuries. Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th century AD. The British Government enquiry took the view the cause was not scrapie as had originally been postulated, and was some event in the 1970s that it was not possible to identify.Findings published in PLoS Pathogens (September 12, 2008) suggest that mad cow disease also is caused by a genetic mutation within a gene called Prion Protein Gene. The research shows, for the first time, that a 10-year-old cow from Alabama with an atypical form of bovine spongiform encephalopathy had the same type of prion protein gene mutation as found in human patients with the genetic form of CreutzfeldtJakob disease, also called genetic CJD for short. Besides having a genetic origin, other human forms of prion diseases can be sporadic, as in sporadic CJD, as well as foodborne. That is, they are contracted when people eat products contaminated with mad cow disease. This form of Creutzfeldt-Jakob disease is called variant CJD.Epidemic in British cattleCattle are normally herbivores. In nature, cattle eat grass. In modern industrial cattle-farming, various commercial feeds are used, which may contain ingredients including antibiotics, hormones, pesticides, fertilizers, and protein supplements. The use of meat and bone meal, produced from the ground and cooked left-overs of the slaughtering process as well as from the cadavers of sick and injured animals such as cattle, sheep, or chickens, as a protein supplement in cattle feed was widespread in Europe prior to about 1987. Worldwide, soya bean meal is the primary plant-based protein supplement fed to cattle. However, soya beans do not grow well in Europe, so cattle raisers throughout Europe turned to the less expensive animal by-product feeds as an alternative. A change to the rendering process in the early 1980s may have resulted in a large increase of the infectious agents in the cattle feed. A contributing factor was suggested to have been a change in British laws that allowed a lower temperature sterilization of the protein meal. While other European countries like Germany required said animal byproducts to undergo a high temperature steam boiling process, this requirement had been eased in Britain as a measure to keep prices competitive. Later the British Inquiry dismissed this theory saying "changes in process could not have been solely responsible for the emergence of BSE, and changes in regulation were not a factor at all."The first animal to fall ill with the disease occurred in 1984 in Britain, lab tests the following year indicated the presence of BSE; it was only in November 1986 that the British Ministry of Agriculture accepted it had a new disease on its hands. Subsequently, 165 people (up until October 2009) acquired and died of a disease with similar neurological symptoms subsequently called vCJD, or (new) variant Creutzfeldt-Jakob disease. This is a separate disease from 'classical' CreutzfeldtJakob disease, which is not related to BSE and has been known about since the early 1900s. Three cases of vCJD occurred in people who had lived in or visited Britain one each in Ireland, Canada and the United States. There is also some concern about those who work with (and therefore inhale) cattle meat and bone meal, such as horticulturists, who use it as fertilizer. Up to date statistics on all types of CJD are published by the National Creutzfeldt-Jakob Disease Surveillance Unit (NCJDSU) in Edinburgh.For many of the vCJD patients, direct evidence exists that they had consumed tainted beef, and this is assumed to be the mechanism by which all affected individuals contracted it. Disease incidence also appears to correlate with slaughtering practices that led to the mixture of nervous system tissue with hamburger and other beef. It is estimated that 400,000 cattle infected with BSE entered the human food chain in the 1980s. Although the BSE epizootic was eventually brought under control by culling all suspect cattle populations, people are still being diagnosed with vCJD each year (though the number of new cases currently has dropped to fewer than 5 per year). This is attributed to the long incubation period for prion diseases, which are typically measured in years or decades. As a result the extent of the human vCJD outbreak is still not fully known.The scientific consensus is that infectious BSE prion material is not destroyed through normal cooking procedures, meaning that contaminated beef foodstuffs prepared "well done" may remain infectious.In 2004 researchers reported evidence of a second contorted shape of prions in a rare minority of diseased cattle. If valid, this would imply a second strain of BSE prion. Very little is known about the shape of disease-causing prions, because their insolubility and tendency to clump thwarts application of the detailed measurement techniques of structural biology. But cruder measures yield a "biochemical signature" by which the newly discovered cattle strain appears different from the familiar one, but similar to the clumped prions in humans with traditional CJD Creutzfeldt-Jakob Disease. The finding of a second strain of BSE prion raises the possibility that transmission of BSE to humans has been underestimated, because some of the individuals diagnosed with spontaneous or "sporadic" CJD may have actually contracted the disease from tainted beef. So far nothing is known about the relative transmissibility of the two disease strains of BSE prion.Penyakit Creutzfeldt-JakobPenyebabPenyakit ensefalopati spongiform menular ini disebabkan oleh prion, sehingga sering disebut sebagai penyakit prion. Penyakit prion lainnya termasuk Sindrom Gerstmann-Strussler-Scheinker (GSS), insomnia familial fatal dan kuru pada manusia, juga ensefalopati spongiform sapi yang umum dikenal sebagai penyakit sapi gila, chronic wasting disease (CWD) pada rusa, dan scrapie pada domba.Prion yang dipercaya menyebabkan Creutzfeldt-Jakob memperlihatkan setidaknya 2 konformasi yang stabil. Konformasi dalam keadaan asli itu larut air dan ada dalam sel yang sehat. Sampai 2006, fungsi biologisnya tak diketahui. Keadaan konformatif lainnya kurang larut air dan mudah membentuk agregat protein.Orang juga bisa terjangkit Creutzfeldt-Jakob melalui mutasi gen (perlu didefinisikan), yang hanya terjadi dalam 5-10% dari semua kasus.Prion Creutzfeldt-Jakob berbahaya karena meningkatkan pelipatan protein asal ke dalam keadaan sakit, yang menyebabkan meningkatnya prion tak larut pada sel yang terjangkit. Massa protein yang salah lipat ini mengacaukan fungsi sel dan menyebabkan kematiannya. Mutasi pada gen untuk protein prion bisa menyebabkan kesalahan lipat sebagian besar regio alfa-heliks ke lembar beta yang terlipat. Perubahan konformasi ini melumpuhkan kemampuan protein mengalami pencernaan. Sekali prion ditransmisikan, protein cacat itu menyerang otak dan diproduksi di putaran umpan balik yang disokong sendiri, menyebabkan penyebaran eksponensial prion, kematian dalam beberapa bulan, meski beberapa orang diketahui hidup selama-lamanya 2 tahun.Insidensi dan prevalensiMeski merupakan penyakit prion yang paling umum pada manusia, Creutzfeldt-Jakob masih jarang dan hanya terjadi pada sekitar 1:1.000.000 orang, yang biasanya menjangkiti orang antara usia 4575, kebanyakan muncul pada orang antara usia 6065. Pengecualian dalam hal ini adalah Creutzfeldt-Jakob varian (vCJD) yang kini dikenali, yang terjadi pada orang berusia muda. Creutzfeldt-Jakob terjadi sedunia dalam tingkat 1:1.000.000 penduduk per tahun. Penyakit ini paling banyak ditemukan pada pasien antara usia 5565, namun kasus ini dapat terjadi pada orang yang berusia lebih dari 90 tahun dan kurang dari 55 tahun.GejalaGejala pertama Creutzfeldt-Jakob adalah demensia yang berlangsung cepat, menimbulkan kehilangan ingatan, perubahan kepribadian dan halusinasi, yang disertai dengan masalah fisik seperti menurunnya kecakapan berbicara, gerakan tertegun-tegun (mioklonus), disfungsi keseimbangan koordinasi (ataksia), perubahan gaya berjalan, postur yang kaku, dan serangan jantung. Durasi penyakit ini bervariasi, namun Creutzfeldt-Jakob yang sporadik (tak diwarisi) bisa fatal dalam beberapa bulan bahkan minggu (Johnson, 1998). Pada beberapa orang, gejala itu bisa berlanjut selama beberapa tahun. Pada sebagian besar pasien, gejala tersebut diikuti dengan gerakan tak sadar dan munculnya pelacakan elektroensefalogram diagnostik khas.Gejala Creutzfeldt-Jakob disebabkan oleh kematian sel saraf otak yang berkelanjutan, yang dikaitkan dengan bertambahnya protein prion abnormal. Saat jaringan otak penderita Creutzfeldt-Jakob diperiksa di bawah mikroskop, banyak lubang kecil terlihat di mana keseluruhan area sel saraf mati. Kata 'spongiform' pada 'ensefalopati spongiform menular' merujuk pada kemunculan 'pori' pada jaringan otak.DiagnosisDiagnosis Creutzfeldt-Jakob dicurigai bila ada gejala klinik dan tanda yang khas seperti demensia yang berlangsung cepat dengan mioklonus. Pengamatan lanjutan kemudian dapat dilakukan untuk mendukung diagnosis termasuk Elektroensefalografi sering ada gambaran paku trifasik yang khas Analisis cairan serebrospinal untuk protein 14-3-3 MRI otak sering menunjukkan intensitas sinyal tinggi di nucleus caudatus dan putamen secara bilateral pada gambar diapit T2.CJD klasikCJD varian

Usia kematian rata-rata68 tahun28tahun

Durasi sakit rata-rata4-5bulan13-14bulan

Tanda dan gejala klinikDemensia; tanda neurologis awalGejala psikiatri/perilaku mencolok; disestesias nyeri; Tanda neurologis yang terlambat

Gelombang elekteroensefalogram yang tajam secara berkalaSering adaSering tiada

Hiperintensitas sinyal di nucleus caudatus dan putamen pada difusi apit dan FLAIR MRISering adaSering tiada

"Tanda pulvinar" di MRITak dilaporkanAda dalam >75% kasus

Analisis imunohistokimia jaringan otakAkumulasi bervariasiAkumulasi protein prion resisten proteaseyang mengancam

Keberadaan agen di jaringan getah beningTak mudah dideteksiMudah dideteksi

Pertambahan rasio glikoform pada analisis imunoblot protein prion resisten proteaseTak dilaporkanAkumulasi protein prion resisten proteaseyang mengancam

Gambar Diffusion Weighted Imaging (DWI) paling sensitif. 24% kasus DWI hanya menunjukkan hiperintensitas korteks; 68% abnormalitas korteks dan subkorteks; dan 5% hanya anomali subkorteks Keterlibatan talamus dapat ditemukan pada sCJD (Creutzfeldt-Jakob sporadik), malahan lebih kuat dan konstan daripada vCJD.Dalam sepertiga pasien sCJD, endapan "protein prion (scrapie)," PrPSc, dapat ditemukan di otot rangka dan/atau limpa. Diagnosis vCJD dapat didukung dengan biopsi amandel, yang mengandung PrpSc dalam jumlah banyak; namun, biopsi jaringan otak lebih bersifat menentukan.PenularanProtein yang cacat dapat ditularkan oleh produk hormon pertumbuhan manusia (hGH), cangkoqan kornea, cangkoqan dura atau implan elektrode (bentuk yang didapat atau iatrogenik: iCJD); dapat diwarisi (bentuk herediter atau familial: fCJD); atau muncul untuk pertama kalinya pada pasien (bentuk sporadik: sCJD). Dalam bentuk herediter, sebuah mutasi terjadi pada gen untuk PrP, PRNP. 10-15% kasus Creutzfeldt-Jakob diwarisi. (CDC)Penyakit itu telah diketahui diakibatkan dari penggunaan HGH yang diambil dari kelenjar pituitari kadaver yang mati akibat penyakit Creutzfeldt-Jakob,[14] meski insidensi penyebabnya yang diketahui cukup kecil (sampai April 2004). Risiko infeksi melalui penggunaan HGH kadaver di AS hanya berakhir saat pengobatan itu dihentikan pada tahun 1985.Diperkirakan manusia dapat terjangkit penyakit ini dengan mengkonsumsi bahan dari hewan yang terinfeksi penyakit ini yang dari jenis sapi. Sejauh ini, satu-satunya kasus yang dicurigai muncul adalah vCJD.Dapat juga ditularkan melalui transfusi darah.