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Multisystem Proteinopathy
Multisystem proteinopathy (MSP) is a dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone, and/or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), inclusion body myopathy (IBM), Paget's disease of bone (PDB), or as a combination of these disorders. Historically, several different names have been used to describe MSP, most commonly "inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD)" or "inclusion body myopathy with frontotemporal dementia, Paget's disease of bone, and amyotrophic lateral sclerosis (IBMPFD/ALS)." However, IBMPFD and IBMPFD/ALS are now considered outdated classifications and are more properly referred to as MSP, as the disease is clinically heterogeneous and its phenotypic spectrum extends beyond IBM, PDB, FTD, and ALS to include motor neuron disease, Parkinson's disease features, and ataxia featur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HNRNPA2B1
Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the ''HNRNPA2B1'' gene. Structure ''HNRNPA2B1'' gene contains 12 exons, including a B1 protein specific 36-nucleotide mini-exon. The entire length of intron/exon organization of ''HNRNPA2B1'' is identical to that of the '' HNRNPA1'' gene which indicates a common origin by gene duplication. Function This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pleiotropic
Pleiotropy () is a condition in which a single gene or genetic variant influences multiple phenotypic traits. A gene that has such multiple effects is referred to as a ''pleiotropic gene''. Mutations in pleiotropic genes can impact several traits simultaneously, often because the gene product is used in various cells and affects different biological targets through shared signaling pathways. Pleiotropy can result from several distinct but potentially overlapping mechanisms, including gene pleiotropy, developmental pleiotropy, and selectional pleiotropy. Gene pleiotropy occurs when a gene product interacts with multiple proteins or catalyzes different reactions. Developmental pleiotropy refers to mutations that produce several phenotypic effects during development. Selectional pleiotropy occurs when a single phenotype influences evolutionary fitness in multiple ways (depending on factors such as age and sex). There are also three main types of genetic pleiotropic effects when ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control Skeletal muscle, voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle Spasticity, stiffness, Fasciculation, twitches, Muscle weakness, weakness, and Muscle atrophy, wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with cognitive disorder, thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as ''limb-onset'' (b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Frontotemporal Dementia
Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal lobe, frontal and temporal lobes. Men and women appear to be equally affected. FTD generally presents as a behavioral or language disorder with gradual onset. Signs and symptoms tend to appear in late adulthood, typically between the ages of 45 and 65, although it can affect people younger or older than this. There is currently no cure or approved symptomatic treatment for FTD, although some Off-label use, off-label drugs and behavioral methods are prescribed. Features of FTD were first described by Arnold Pick between 1892 and 1906. The name ''Pick's disease'' was coined in 1922. This term is now reserved only for the behavioral variant of FTD, in which characteristic Pick bodies and Pick cells are present. These were first described by Alois Alzheimer in 1911. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inclusion Body Myopathy
Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles. HIBMs are a group of muscle wasting disorders that are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also been identified in other minorities throughout the world, including those of Asian, European, and South American, and Middle Eastern descent. In Japan and other East Asian countries, this disorder is known as distal myopathy with rimmed vacuoles (DMRV). IBM2 causes progressive muscle w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Paget's Disease Of Bone
Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving Bone remodeling, cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive Osteoclast, bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, bone fractures, fracture or arthritis of associated joints. The exact cause is unknown, although leading theories indicate both genetic and acquired factors (see #Causes, Causes). Paget's disease may affect any one or several bones of the body (most commonly pelvis, tibia, femur, lumbar vertebrae, and skull), but never the entire skeleton, and does not spread from bone to bone. Rarely, a bone affected by Paget's disease can transform into a Osteosarcoma, malignant bone cancer. As the disease often affects people diffe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ataxia
Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements, that indicates dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum. These nervous system dysfunctions occur in several different patterns, with different results and different possible causes. Ataxia can be limited to one side of the body, which is referred to as hemiataxia. Friedreich's ataxia has gait abnormality as the most commonly presented symptom. Dystaxia is a mild degree of ataxia. Types Cerebellar The term cerebellar ataxia is used to indicate ataxia due to dysfunction of the cerebellum. The cerebellum is responsible for integrating a significant amount of neural information that is used to coordinate smoothly ongoing movements and to participate in motor planning. A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the 26S proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TDP-43
Transactive response DNA binding protein 43 kDa (TAR DNA-binding protein 43 or TDP-43) is a protein that in humans is encoded by the ''TARDBP'' gene. Structure TDP-43 is 414 amino acid residues long. It consists of four domains: an N-terminal domain spanning residues 1–76 (NTD) with a well-defined fold that has been shown to form a dimer or oligomer; two highly conserved folded RNA recognition motifs spanning residues 106–176 (RRM1) and 191–259 (RRM2), respectively, required to bind target RNA and DNA; an unstructured C-terminal domain encompassing residues 274–414 (CTD), which contains a glycine-rich region, is involved in protein-protein interactions, and harbors most of the mutations associated with familial amyotrophic lateral sclerosis. The entire protein devoid of large solubilising tags has been purified. The full-length protein is a dimer. The dimer is formed due to a self-interaction between two NTD domains, where the dimerisation can be propagated to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HNRNPA1
Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the ''HNRNPA1'' gene. Mutations in hnRNP A1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy. Function This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi- RRM domains that bind to RNAs in the N-terminal domain which are pivotal for RNA specificity and binding. The protein also has a glycine rich arginine-glycin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Valosin-containing Protein
Valosin-containing protein (VCP) or transitional endoplasmic reticulum ATPase (TER ATPase) also known as p97 in mammals and CDC48 in '' S. cerevisiae,'' is an enzyme that in humans is encoded by the ''VCP'' gene. The TER ATPase is an ATPase enzyme present in all eukaryotes and archaebacteria. Its main function is to segregate protein molecules from large cellular structures such as protein assemblies, organelle membranes and chromatin, and thus facilitate the degradation of released polypeptides by the multi-subunit protease proteasome. VCP/p97/CDC48 is a member of the AAA+ (extended family of ATPases associated with various cellular activities) ATPase family. Enzymes of this family are found in all species from bacteria to humans. Many of them are important chaperones that regulate folding or unfolding of substrate proteins. VCP is a type II AAA+ ATPase, which means that it contains two tandem ATPase domains (named D1 and D2, respectively) (Figure 1). The two ATPase domai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Optineurin
Optineurin is a protein that in humans is encoded by the ''OPTN'' gene. Function This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Interactions Optineurin has been shown to interact with Huntingtin Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
