Table 2.

Modulators of autophagy in neuronal disease models

Compound	Proposed target and mechanism	Model system and selected references
Bafilomycin A1	Autophagy inhibition Inhibition of the vacuolar-type ATPase Disrupts lysosomal acidification and prevents autophagosome-lysosome fusion	Neuronal cell models: Shacka et al., 2006; Bains et al., 2009 Mouse models: Ebrahimi-Fakhari et al., 2011; Klucken et al., 2012
Carbamazepine	Autophagy induction Voltage-gated Na2+ channel inhibitor Lowers inositol and inositol-1,4,5-triphosphate levels	Neuronal cell models: Williams et al., 2008; Xiong et al., 2011 IPSC-derived neuronal cells: Maetzel et al., 2014 Mouse models: Wang et al., 2012a; Li et al., 2013
(Hydroxy-) Chloroquine	Autophagy inhibition Disrupts lysosomal acidification and prevents autophagosome-lysosome fusion	Neuronal cell models: Boland et al., 2010 Mouse models: Ebrahimi-Fakhari et al., 2011; Vodicka et al., 2014
Clonidine	Autophagy induction Imidazole receptor agonist Lowers cAMP levels	Neuronal cell model: D. melanogaster; zebrafish Williams et al., 2008
Latrepirdine	Autophagy induction mTORC1 inhibition	Neuronal cell model, mouse models: Steele et al., 2013a, 2013b
Lithium	Autophagy induction Inositol monophosphatase inhibitor Lowers inositol and inositol-1,4,5-triphosphate levels	Neuronal cell models: Sarkar et al., 2005; Chang et al., 2011 Mouse models: Sarkar et al., 2005; Fornai et al., 2008; Shimada et al., 2012; Duarte-Silva et al., 2014
Nilotinib	Autophagy induction Abl tyrosine kinase inhibitor Activates AMPK	Mouse models: Hebron et al., 2013; Lonskaya et al., 2014
Rapamycin and rapalogs	Autophagy induction mTORC1 inhibition	Neuronal cell models: Webb et al., 2003; Pan et al., 2008b; Williams et al., 2008 Mouse models: Ravikumar et al., 2004; Menzies et al., 2010; Majumder et al., 2011; Cortes et al., 2012; Viscomi et al., 2012; Jiang et al., 2014
Resveratrol	Autophagy induction Sirtuin-1 activation Activates AMPK	Neuronal cell model: Vingtdeux et al., 2010 Mouse model: Vingtdeux et al., 2010; Shu et al., 2015
Rilmenidine	Autophagy induction Imidazole receptor agonist Lowers cAMP levels	Neuronal cell model: Williams et al., 2008; Rose et al., 2010 Mouse model: Rose et al., 2010
SMER28 and other SMER	Autophagy induction Unknown mechanism, likely mTOR-independent	Neuronal cell model: Tian et al., 2011; D. melanogaster: Sarkar et al., 2007b
Trehalose	Autophagy induction Chemical chaperone	Neuronal cell model: Sarkar et al., 2007a Mouse models: Rodriguez-Navarro et al., 2010; Schaeffer et al., 2012; Castillo et al., 2013; Zhang et al., 2014; He et al., 2015; Li et al., 2015
Valproate	Autophagy induction Myo-inositol-3-phosphate synthase inhibitor Lowers inositol and inositol-1,4,5-triphosphate levels	Neuronal cell model, D. melanogaster: Williams et al., 2008
Verapamil (and other Ca2+-channel blockers)	Autophagy induction L-type Ca2+-channel antagonist Lowers intracellular calcium levels	Neuronal cell model, D. melanogaster; zebrafish: Williams et al., 2008