Table 2.

Summary of HIF-1 inducers and their mechanisms responsible for HIF-1’s neuroprotection in neurodegenerative diseases.

Diseases	Chemicals	Mechanisms of action	Positive effects	Involvement of HIF-1 target genes
ALS	M30	Novel iron chelator; sequestering of ferrous iron, preventing formation of a catalytically active centre in the HIF hydroxylases thereby inducing HIF-1 activation	↑Microvessel formation and blood supply ↑Motor neurotrophy	VEGF and EPO
AD	DFO	Iron chelators; sequestering of ferrous iron, preventing formation of a catalytically active centre in the HIF hydroxylases thereby inducing HIF-1 activation	↑Redox homeostasis ↑Oxygen delivery and supply ↑Glucose uptake	VEGF, EPO, and GLUT-1,3
	M30
PD	Cobalt	Displacing the free ferrous at the active site of hydroxylases thereby inhibiting HIF-1 hydroxylation	↑ DA Synthesis and secretion ↑Iron homeostasis ↑Mitochondria functions	VEGF and EPO
	DFO	Iron chelator; sequestering of ferrous iron, preventing formation of a catalytically active centre in the HIF hydroxylases thereby inducing HIF-1 activation
	FG0041 3,4-DHB	Analogues of 2-oxoglutarate; bind to the active site of HIF hydroxylase, inhibiting HIF hydroxylase
HD	Cobalt	Displacing the free ferrous at the active site of hydroxylases thereby inhibiting HIF-1 hydroxylation	↑Production of ATP and NADPH ↑Glia cells activity
	DFO Clioquinol M30	Iron chelators; sequestering of ferrous iron, preventing formation of a catalytically active centre in the HIF hydroxylases thereby inducing HIF-1 activation