Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease: A focused review

Shokouh Arjmand, Mehran Ilaghi, Ali Karimi Sisakht, Matti Bock Guldager, Gregers Wegener, Anne M Landau, Albert Gjedde*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

2 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ERs) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and ERs potentially pave the way for more effective approaches to AD therapy.

Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Volume135
Issue2
Pages (from-to)115-132
Number of pages18
ISSN1742-7843
DOIs
Publication statusPublished - Aug 2024

Keywords

  • Alzheimer's disease
  • estrogen receptors
  • estrogens
  • glucose metabolism
  • mitochondrial bioenergetics
  • mitochondrial dynamics
  • mitochondrial estrogen receptor
  • mitochondrial function
  • sex differences

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