Autophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation

Article ID	Journal	Published Year	Pages	File Type
8480465	Seminars in Cell & Developmental Biology	2015	34 Pages	PDF

Abstract

Neuronal homeostasis depends on the proper functioning of quality control systems like autophagy. This mechanism is responsible of the clearance of misfolded proteins, aggregates and the turnover of organelles within the neuron. Autophagic dysfunction has been described in many neurodegenerative diseases. It can occur at several steps of the autophagic machinery and can contribute to the formation of intracellular aggregates and ultimately to neuronal death. Accordingly restoring autophagy activity in affected neurons can be an attractive therapeutic approach to fight neurodegeneration. In this review we summarize the present encouraging strategies that have been achieved with pharmacological and genetic treatments aimed to induce neuronal autophagy in experimental models of neurodegenerative diseases.

Keywords

ESCRT GCase PS-1 APP LMP mTORC2 PDD TFEB MTOC PI3P mTORC1 SNARE htt FTLD-U DLB NFT PolyQ CMA phophatidylethanolamine PI3K MMP mitochondria membrane permeabilization phagophore assembly site FDA Lamp-2a mTOR complex 2 LC3 interacting region Aβ mTOR Chaperone-mediated autophagy cAMP Lysosomal membrane permeabilization presenilin 1 SNpc Adenosine Triphosphate ATP Cyclic adenosine monophosphate Alzheimer Autophagy amyotrophic lateral sclerosis amyloid beta Lewy body LIR Alzheimer's disease ALS Huntington's disease Parkinson's disease Parkinson's disease dementia Dementia with Lewy bodies substantia nigra pars compacta Neurodegeneration leucine-rich repeat kinase 2 Rapamycin Food and Drug Administration Ubiquitin-proteasome system endoplasmic reticulum Transcription factor EB phosphatidylinositol 3-phosphate phosphoinositide 3-kinase endosomal sorting complexes required for transport microtubule-organizing center Multiple sclerosis neurofibrillary tangles PAS Huntingtin Huntington mammalian target of rapamycin Parkinson amyloid precursor protein Polyglutamine glucocerebrosidase UPS