Table 1.

Proteins involved in autophagy and their disease modifying role in common neurodegenerative disorders.

Autophagy Signaling Factors	Cellular function(s)	Clinical Relevance	Disease Model
Beclin-1.	Involved in autophagosome formation	Reduced beclin-1 expression in postmortem AD brains22. Beclin-1 sequestration into neuronal intranuclear inclusions in HD patients- reduced beclin-1 function lead to impaired autophagic clearance of mutant htt62. Beclin-1 induction in sporadic ALS spinal cord – believed to promote autophagy66	Beclin-1 deficiency in APP transgenic AD mice leads to Aβ accumulation due to reduced autophagy. Beclin-1 over- expression attenuates this pathological phenotype22. Beclin-1 gene transfer activated autophagy and attenuated neuropathology in α-synuclein transgenic PD mice74. Induction of Beclin-1 in SOD1 ALS mice66.
mTOR (Phosphatidyl kinase-related kinase)	Negatively regulates autophagy	mTOR levels are dramatically increased in AD brains correlating with tau pathology30.	mTOR inhibition induced autophagy with neuroprotective effects in AD mice and in HD flies and mice30, 31, 58. Elevated mTOR levels are observed in α-synuclein transgenic mice75.
LC3	Conversion of LC3I to LC3II is indicative of autophagosome formation.	Marked induction of LC3 in sporadic and familial ALS spinal cords – suggestive of enhanced autophagy67.	LC3-II levels increased in symptomatic SOD1 ALS mice67.
p62/Sequestosome 1	Autophagic adaptor that interacts with LC3.	p62 immunoreactivity observed in neurofibrially tangles of postmortem AD brains76.	p62-dependent PINK1/parkin-mediated autophagy in non neuronal and neuronal cells77. p62-mediated recognition and targeting of mutant SOD1 for autophagic degradation78.
Dynein	Autophagosome-lysosome fusion.	Dynein mutations – familial ALS79.	Dynein-loss-of function caused premature mutant huntingtin aggregate formation in HD flies and mice, increased LC3II in cell and mice models80.
Parkin	An E3 ligase that facilitates mitophagy.	Parkin loss-of-function mutations – Autosomal recessive juvenile PD81.	Parkin mutations fail to ubiquitinate defective mitochondria causing mitophagic deficits44, 45.
PINK1	A mitochondrial serine-threonine kinase involved in mitochondrial fission, mitochondrial quality control, and mitophagy.	PINK1 loss-of-function mutations – Autosomal recessive PD82.	PINK1 loss-of-function promoted mitophagy as a compensatory response47. PINK1 mutants impaired parkin-mediated ubiquitin signaling and recruitment to mitochondria for mitophagy48, 49, 83, 84.