Table 1.

Physiological and deleterious effect of TNF-α signaling in the CNS.

TNF-α Function	References
Neurophysiology (basal expression and acute disease state)
- Development: act as a neurotrophic factor (neuronal apoptosis)	[32]
- Development: facilitate cell migration and proliferation	[58]
- Cognition	[59, 60]
- Synaptic plasticity	[58, 61]
- Astrocytic gliotransmission	[58]
- Ionic homeostasis	[62]
- Protects from excitotoxicity	[63]
- Facilitator of remyelination by promoting oligodendrocyte survival	[64]
- Sleep	[65]
- Food and water intake	[66]
- Anti-neurogenic effect during adult neurogenesis (cultured ippocampal progenitor cells and SVZ progenitor cells)	[67, 68]
- Host defense	[69]
- Restore brain homeostasis and functions during acute inflammation	[34, 45]
Neuropathology (chronic expression in moderate to high amounts)
- Promote excitotoxicity (in association with glutamate)	[63]
- Cause synaptic loss	[58, 61,63]
- Stimulate astrogliosis and microgliosis	[57]
- Exacerbate amyloidogenesis in Alzheimer’s disease	[70–72]
- Participate in multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, ischemia, and other neurological disorders	[32, 34, 73–75]
- Drive HIV-associated dementia	[76]