Cytoskeleton saga: Its regulation in normal physiology and modulation in neurodegenerative disorders

Eur J Pharmacol. 2022 Jun 15:925:175001. doi: 10.1016/j.ejphar.2022.175001. Epub 2022 May 4.

Abstract

Cells are fundamental units of life. To ensure the maintenance of homeostasis, integrity of structural and functional counterparts is needed to be essentially balanced. The cytoskeleton plays a vital role in regulating the cellular morphology, signalling and other factors involved in pathological conditions. Microtubules, actin (microfilaments), intermediate filaments (IF) and their interactions are required for these activities. Various proteins associated with these components are primary requirements for directing their functions. Disruption of this organization due to faulty genetics, oxidative stress or impaired transport mechanisms are the major causes of dysregulated signalling cascades leading to various pathological conditions like Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD) or amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP) or any traumatic injury like spinal cord injury (SCI). Novel or conventional therapeutic approaches may be specific or non-specific, targeting either three basic components of the cytoskeleton or various cascades that serve as a cue to numerous pathways like ROCK signalling or the GSK-3β pathway. An enormous number of drugs have been redirected for modulating the cytoskeletal dynamics and thereby may pave the way for inhibiting the progression of these diseases and their complications.

Keywords: Actin filaments; Cytoskeletal dynamics; Intermediate filaments; Microtubules; Neurodegenerative disorders.

Publication types

  • Review

MeSH terms

  • Cytoskeleton* / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Huntington Disease / metabolism
  • Microtubules* / metabolism
  • Neurodegenerative Diseases* / metabolism

Substances

  • Glycogen Synthase Kinase 3 beta