Map kinase signaling as therapeutic target for neurodegeneration

Pharmacol Res. 2020 Oct:160:105090. doi: 10.1016/j.phrs.2020.105090. Epub 2020 Jul 21.

Abstract

Aging is known to be one of the major risk factors in many neurodegenerative diseases (ND) whose prevalence is estimated to rise in the coming years due to the increase in life expectancy. Examples of neurodegenerative diseases include Huntington's, Parkinson's, and Alzheimer's diseases, along with Amyotrophic Lateral Sclerosis, Spinocerebellar ataxias and Frontotemporal Dementia. Given that so far these ND do not have effective pharmacological therapies, a better understanding of the molecular and cellular mechanisms can contribute to development of effective treatments. During the previous decade, the data indicated that dysregulation of MAP kinases [which included c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38] are associated with several stages of the inflammatory process which in turn contributes to age-related neurodegenerative diseases. This evidence suggests that control of inflammation through regulation of MAP kinase could be a worthwhile approach against neurodegenerative diseases. In this review we summarize the pathways of MAP kinase signal transduction and different pharmacological inhibitors that can be used in its modulation against ND.

Keywords: Alzheimer’s diseases; Flavonoids; MAPK pathway; Neurodegeneration; Neuroinflammation; Parkinson’s disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Central Nervous System / drug effects*
  • Central Nervous System / enzymology
  • Central Nervous System / pathology
  • Central Nervous System / physiopathology
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Targeted Therapy
  • Nerve Degeneration*
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases