Neurodegenerative diseases in the era of targeted therapeutics: how to handle a tangled issue

Molecular and Cellular Neurosciences
George K Tofaris, Anthony H V Schapira

Abstract

Neurodegenerative diseases are age-related and relentlessly progressive with increasing prevalence and no cure or lasting symptomatic therapy. The well-recognized prodromal phase in many forms of neurodegeneration suggests a prolonged period of neuronal compensated dysfunction prior to cell loss that may be amenable to therapeutic intervention. Although most efforts to date have been focused on misfolded toxic proteins, it is now clear that widespread changes in protein homeostasis occur early in these diseases and understanding this fundamental biology is key to the design of targeted therapies. What has emerged from molecular genetics and animal studies is a previously less appreciated association of neurodegenerative diseases with defects in the molecular regulation of protein trafficking between cellular organelles, especially the intricate network of endosomes, lysosomes, autophagosomes and mitochondria. Here we summarized the broader concepts that stemmed from this Special Issue on "Protein Clearance in Neurodegenerative diseases: from mechanisms to therapies". This article is part of a Special Issue entitled 'Neuronal Protein'.

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Citations

Mar 12, 2016·Expert Opinion on Drug Delivery·Yahya E ChoonaraViness Pillay
Oct 29, 2018·Journal of Biomedical Materials Research. Part a·Timothy M BrenzaGeorgette D Kanmogne
Nov 5, 2016·Chemical Biology & Drug Design·Razieh HosseiniOmidreza Firuzi
Oct 25, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Timothy M BrenzaBalaji Narasimhan

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An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.