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.

Abstract: Treatment of microglial cells with nicotine and THC synergistically attenuate the microglial activation. Using microglial activation, the combination of THC and nicotine interact synergistically reduced LPS induced TNF-? release, showing that the combination of THC and nicotine clinically have greater efficacy in reducing neuroinflammation with less side effects than either drug given alone. CD40 signaling was found critically involved in pathological activation of microglial cells. This invention is also relevant to peripheral inflammation as well thru macrophages. In addition, other cannabinoids and other nicotinic-like medications currently in development are also covered under this discovery.

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.