Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The cause is unknown and no effective treatment currently exists. For ALS, there is only a drug Riluzole and a promising substance arimoclomol. The overlap between ALS and FTD occurs at clinical, genetic, and pathological levels. The majority of ALS cases are sporadic (SALS) and a subset of patients has an inherited form of the disease, familial ALS (FALS), with a common SOD1 mutation, also present in SALS. A few of the mutant genes identified in FALS have also been found in SALS. Recently, hexanucleotide repeat expansions in C9ORF72 gene were found to comprise the largest fraction of ALS- and FTD-causing mutations known to date. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the pathological protein of FALS, SALS and, less frequently, FTD. The less frequent TDP-43 pathology in other forms of familial FTD has been linked to a range of mutations in GRN, FUS/TLS, rarely VCP, and other genes. TDP-43 and FUS/TLS have striking structural and functional similarities, most likely implicating altered RNA processing as a major event in ALS pathogenesis. The clinical overlap of the symptoms of FTD and ALS is complemented by overlapping neuropathology, with intracellular inclusions composed of microtubule-associated protein tau, TDP-43 and less frequently FUS, or unknown ubiquitinated proteins. Furthermore, new therapeutic approaches continue to emerge, by targeting SOD1, TDP-43 or GRN proteins. This review addresses new advances that are being made in our understanding of the molecular mechanisms of both diseases, which may eventually translate into new treatment options.
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PMID:Molecular basis of ALS and FTD: implications for translational studies. 2675 60

Liquid-liquid phase separation (LLPS) and phase transition (LLPT) of proteins and nucleic acids have emerged as a new paradigm in cell biology. Here we will describe the recent findings about LLPS and LLPT, including the molecular and physical determinants leading to their formation, the resulting functions and their implications in cell physiology and disease. Amyloid aggregation is implicated in many neurodegenerative diseases and cancer, and LLPS of proteins involved in these diseases appear to be related to their function in different cell contexts. Amyloid formation would correspond to an irreversible liquid-to-solid transition, as clearly observed in the case of PrP, TDP43, FUS/TLS and tau protein in neurodegenerative pathologies as well as with the mutant tumor suppressor p53 in cancer. Nucleic acids play a modulatory effect on both LLPS and amyloid aggregation. Understanding the molecular events regulating how the demixing process advances to solid-like fibril materials is crucial for the development of novel therapeutic strategies against cancer and neurodegenerative maladies.
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PMID:Liquid-liquid phase transitions and amyloid aggregation in proteins related to cancer and neurodegenerative diseases. 3192 29