The Common Cellular Events in the Neurodegenerative Diseases and the Associated Role of Endoplasmic Reticulum Stress

Soojeong Kim, Doo Kyung Kim, Seho Jeong, Jaemin Lee

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

Abstract

Neurodegenerative diseases are inseparably linked with aging and increase as life expectancy extends. There are common dysfunctions in various cellular events shared among neurogenerative dis-eases, such as calcium dyshomeostasis, neuroinflammation, and age-associated decline in the autophagy-lysosome system. However, most of all, the prominent pathological feature of neurodegenerative diseases is the toxic buildup of misfolded protein aggregates and inclusion bodies accompanied by an impairment in proteostasis. Recent studies have suggested a close association between endoplasmic retic-ulum (ER) stress and neurodegenerative pathology in cellular and animal models as well as in human patients. The contribution of mutant or misfolded protein-triggered ER stress and its associated signaling events, such as unfolded protein response (UPR), to the pathophysiology of various neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease, amyotrophic lateral sclerosis, and prion disease, is described here. Impaired UPR action is commonly attributed to exacerbated ER stress, pathogenic protein aggregate accumulation, and deteriorating neurodegenerative pathologies. Thus, activating certain UPR components has been shown to alleviate ER stress and its associated neurodegeneration. However, uncontrolled activation of some UPR factors has also been demonstrated to worsen neurodegenerative phenotypes, suggesting that detailed molecular mechanisms around ER stress and its related neurodegenerations should be understood to develop effective therapeutics against aging-associated neurological syndromes. We also discuss current therapeutic endeavors, such as the development of small molecules that selectively target individual UPR components and address ER stress in general.

Original languageEnglish
Article number5894
JournalInternational Journal of Molecular Sciences
Volume23
Issue number11
DOIs
StatePublished - 1 Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Alzheimer’s disease
  • ER stress
  • Huntington’s disease
  • Parkin-son’s disease
  • amyotrophic lateral sclerosis
  • endoplasmic reticulum
  • misfolded protein
  • neurodegenerative disease
  • prion disease
  • unfolded protein response

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