Abstract: The invention relates to treatment of neurodegenerative diseases with JAK/STAT pathway inhibitors to eliminate extracellular cell signaling events leading to cell cycle abrogation and/or apoptosis. Primary neurons were administered neurotoxic proteins, such as gp120, Tat, or gp120 and Tat, with or without IFN-? added, resulting in neuronal death, and simulated neurodegenerative diseases. The neurodegenerative disease is treated using a JAK/STAT pathway inhibitor, including (-)-epigallocatechin-3-gallate (EGCG), to modulate JAK1 or STAT1 phosphorylation, resulting in resistance to gp120 or Tat neurotoxicity. The invention may be used to treat neurons afflicted with HIV-associated Dementia, multiple sclerosis, Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, or Pick's Disease, and may act in conjunction with antiviral treatment, like HAART.