Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation

Table 2 Dysregulated PI3K-AKT signaling in neurodegenerative diseases

Disease	Signaling defects	Study type	Outcomes	Key references
Alzheimer’s disease	Polymorphic mutations within INPP5D, presumably altering negative regulation of PI3K-AKT signaling	Clinical	Risk factor for late-onset AD Associated with disease-related neuropathology	[151,152,153,154]
Alzheimer’s disease		Preclinical—mouse	Reduced plaque uptake by microglia	[155]
Huntington’s disease	Elevated AKT proteins in lymphoblasts and Akt1 in monocytes	Clinical	Associated with HD development Increased IL-1β and TNF-α levels Microgliosis	[156, 157] [158]
Huntington’s disease		Preclinical—mouse	Increased IL-1β and TNF-α levels Microgliosis	[159]
Parkinson’s disease	Abnormal PINK1 activity, altering PI3K-AKT signaling	Clinical	Recessively inherited form of PD	[160, 161]
Parkinson’s disease	Abnormal PINK1 activity, altering PI3K-AKT signaling	Preclinical—mouse	Altered AKT activity in microglia and induces a pro-inflammatory response	[162, 163]

AD Alzheimer’s disease, AKT protein kinase B, HD Huntington’s disease, IL-1β interleukin 1 beta, INPP5D inositol polyphosphate-5-phosphatase D, PD Parkinson’s disease, PI3K phosphoinositide 3-kinase, PINK1 PTEN-induced serine/threonine–protein kinase 1, TNF-α tumor necrosis factor-alpha