Скачать с ютуб Beta amyloid and Tau proteins (transglutaminase substrates) NIA в хорошем качестве

Beta amyloid and Tau proteins (transglutaminase substrates) NIA

FOTGCREN HYPOTHESIS: A tale of bugs and foods: Hwp1 versus gluten and casein (v3)    • A tale of bugs and foods: Hwp1 versus...   GROSSO 2012 http://www.ncbi.nlm.nih.gov/pubmed/22... Tissue transglutaminase (TG2) is implicated in a number of neurodegenerative disorders including Huntington's (HD), Alzheimer's (AD), and Parkinson's diseases (PD) based on several lines of evidence (4): First, TG2 is found throughout most brain regions, particularly in neurons, and accounts for the majority of transglutaminase activity in the mouse brain (4). Second, the pathophysiology of all these diseases includes the formation of insoluble aggregates, and the covalent cross-linking of pathogenic proteins by TG2 is effectively irreversible and leads to the formation of protein polymers (4). Third, conditions that promote the cross-linking activity of TG2 intracellularly, such as low GTP and high calcium levels, are frequently met in damaged cells in neurodegenerative diseases where there is energy depletion and loss of calcium homeostasis. Increased calcium concentration can also induce translocation of TG2 to the nucleus where it can repress transcription of potentially protective genes (4). Fourth, oxidative damage, which is a well-known occurrence in these diseases, can make proteins better substrates for TG2 (4). And fifth, the role of TG2 in autophagy may be another link between TG2 and neurodegenerative diseases considering the dysregulated autophagy in the pathogenesis of these disorders (4). This line of reasoning has led to the notion that in neurodegenerative diseases, neuronal damage either due to environmental insults or genetic predisposition leads to conditions conducive to TG2 activation. TG2 then begins to cross-link susceptible substrates into conformations that may be toxic or may prevent important proteins from performing their biological functions. This, in turn, exacerbates the damage to neurons, preventing them from recovering from the initial insult and leading to cell death. To examine this hypothesis, the role of TG2 has been studied in neurodegenerative diseases, and considerable evidence has built up suggesting that it does play a role in these disorders (4). Abnormal protein aggregates and the accumulating evidence that certain forms of these aggregates can be neurotoxic (4). Factors that promote the formation of these aggregates have been the subject of intense investigations with the objective of identifying interventions that can slow the progressive disease process. One of these factors is the crosslinking of pathogenic proteins into toxic higher order oligomers by the enzymatic activity of TG2 (4). Some proteins involved in neurodegenerative diseases can also propagate across neurons (4).