Targeting of neuroinflammation, oxidative stress, and synaptic dysfunction by vinpocetine in alzheimer's disease: a comprehensive appraisal.

Alzheimer disease (AD) is a neurodegenerative disease presented with progressive memory loss and cognitive impairment. Deposition of extracellular amyloid beta (Aβ) peptide and intracellular neurofibrillary tangles (NFTs) are the hallmarks of AD neuropathology. Progressive accumulation of Aβ and NFTs results in the development of inflammation/ neuroinflammation, oxidative stress, synaptic failure, neuronal apoptosis, and the development of AD. However, no single drug is effective as disease modifying treatment for AD, as many cellular and molecular signaling pathways beyond Aβ and NFTs are involved in AD neuropathology. Mounting evidences indicated that phosphodiesterase enzymes (PDEs) mainly PDE1 are involved in AD neuropathology. PDEs are intricate in the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are reduced in AD. Consequently, this review aims to revise the role of PDEs, and PDE1 selective inhibitor vinpocetine (VPN) in AD neuropathology. VPN by its anti-inflammatory and antioxidant effects can reduce inflammatory and oxidative stress in AD correspondingly. At molecular levels, VPN by targeting peroxisome proliferator activated receptor γ coactivator 1 α (PGC1α), brain derived neurotrophic factor (BDNF) and SIRT1 can mitigate AD neuropathology. Despite of these evidences, however there is limited clinical evidence for the efficacy of VPN in AD. Therefore, large-prospective clinical studies are warranted in this regard.