DS9 Document EFTA01049971

From• To: Jeffrey Epstein <[email protected]> Subject: aggregation and degeneration Date: Mon, 10 Apr 2017 23:41:29 +0000 I think these all have a more common origin than we thought...involves vagus and stress to the system. Different stressors hit different parts of the system. More when I see you. The approach to prevent and treat would be radically different from what is happening now. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prlon diseases are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation. The aggregates usually consist of fibers containing misfolded protein with a ,eta-sheet conformation, termed amylold. There Is partial but not perfect overlap among the cells in which abnormal proteins are deposited and the cells that degenerate. The most likely explanation is that inclusions and other visible protein aggregates represent an end stage of a molecular cascade of several steps, and that earlier steps in the cascade may be more directly tied to pathogenesis than the inclusions themselves. For several diseases, genetic variants assist in explaining the pathogenesis of the more common sporadic forms and developing mouse and other models. There is now increased understanding of the pathways Involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity. These are leading to approaches toward rational therapeutics. EFTA01049971