Table 1 Signaling pathways with established links to HD

Mutant Htt affects calcium signaling in primary cultures of medium spiny neurons from HD mouse models by increasing the influx of extra-cellular Ca²⁺ and the intra-cellular release of Ca²⁺ from ER [63, 64]

25

0.01

Induction of mutant Htt in PC12 cells leads to activation of MAPK signaling via ERK and JNK. ERK phosphorylation correlates with reduced apoptosis, whereas JNK activity correlates with Htt-associated cell death in a striatal HD cell line [65]

42

0.0002

The insulin signaling pathway promotes survival of striatal cells (transfected with mutant Htt) through neuroprotective effects of Akt activation and triggers autophagy mediated clearance of huntingtin via insulin receptor substrate-2 in HD cell model [66]

20

0.02

Inhibition of mTOR by rapamycin or by sequestration into aggregates induces autophagy in HD cell model and reduces neurodegeneration in HD fly and mouse model [62]

17

0.01