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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Trends Neurosci. 2010 Oct 12;33(12):541–549. doi: 10.1016/j.tins.2010.09.001

Table 2.

Autophagy modulators and their disease modifying action in common neurodegenerative disorders.

Autophagy Modulators Mode of Action Disease Pathology Modifier
Rapamycin CCI-779 (rapamycin analog)

Glucose transporter (GLUT1)		 Inhibit mTOR activating autophagy

Raise intracellular glucose or glucose-6- phosphate		 Clearance of mutant α-synuclein in cells37.
Reduces Aβ levels and associated cognitive deficits31.
Decreased mutant aggregate-prone tau proteins in flies85.
Reduced toxicity of polyglutamine expansion in fly and mouse HD models58, 86, 87.
Small molecule enhancers (SMERs) mTOR-independent autophagic inducers Mutant htt clearance86.
Mutant A53T α-synuclein reduction86.
Lithium, Sodium valproate, carbamazepine, L-690, 330. Inositol lowering agents – inhibit inositol monophosphatase (IMPase)
mTOR-independent autophagic inducer		 Increased survival in ALS mouse88.
Improved outcome in ALS clinical trial89.
Mutant Htt aggregation/toxicity reduction90.
Trehalose disaccharide, Minoxidil, Clonidine mTOR-independent autophagic inducer Increased autophagic flux, clearance of mutant htt and α-synuclein mutants91, 92.
Ameliorates dopaminergic and tau pathology93.
Combination Therapy: Rapamycin + Trehalose/Calpastatin/SMERs mTOR-dependent and mTOR-independent targets Additive effect-enhanced autophagic clearance of protein aggregates91, 92.