Potential Drug Candidates to Treat TRPC6 Channel Deficiencies in the Pathophysiology of Alzheimer's Disease and Brain Ischemia

Cells. 2020 Oct 24;9(11):2351. doi: 10.3390/cells9112351.

Abstract

Alzheimer's disease and cerebral ischemia are among the many causative neurodegenerative diseases that lead to disabilities in the middle-aged and elderly population. There are no effective disease-preventing therapies for these pathologies. Recent in vitro and in vivo studies have revealed the TRPC6 channel to be a promising molecular target for the development of neuroprotective agents. TRPC6 channel is a non-selective cation plasma membrane channel that is permeable to Ca2+. Its Ca2+-dependent pharmacological effect is associated with the stabilization and protection of excitatory synapses. Downregulation as well as upregulation of TRPC6 channel functions have been observed in Alzheimer's disease and brain ischemia models. Thus, in order to protect neurons from Alzheimer's disease and cerebral ischemia, proper TRPC6 channels modulators have to be used. TRPC6 channels modulators are an emerging research field. New chemical structures modulating the activity of TRPC6 channels are being currently discovered. The recent publication of the cryo-EM structure of TRPC6 channels should speed up the discovery process even more. This review summarizes the currently available information about potential drug candidates that may be used as basic structures to develop selective, highly potent TRPC6 channel modulators to treat neurodegenerative disorders, such as Alzheimer's disease and cerebral ischemia.

Keywords: Alzheimer’s disease; TRPC6; cerebral ischemia; pharmaceutical agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / etiology*
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Disease Management
  • Disease Susceptibility
  • Drug Discovery
  • Gene Expression Regulation / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Risk Factors
  • Signal Transduction / drug effects
  • TRPC6 Cation Channel / antagonists & inhibitors
  • TRPC6 Cation Channel / deficiency*
  • TRPC6 Cation Channel / genetics
  • TRPC6 Cation Channel / metabolism

Substances

  • TRPC6 Cation Channel
  • TRPC6 protein, human