Back to all available

The Interplay between Mitophagy and Ferroptosis in Alzheimer's Disease: Mechanisms and Therapeutic Implications

neuroscience
cognitive-disorders
geriatrics
neurology

Abstract

Alzheimer's disease (AD) ischaracterizedby the deposition of amyloid-β (Aβ) and T au neurofibrillary tangles. In recent years, mitophagy, the selective clearance of damaged mitochondria, and ferroptosis, an iron-dependent form of programmed cell death,have emerged as pivotal driversof neurodegeneration in AD. This review systematicallyoutlinesthe molecular mechanisms of mitophagy and ferroptosis,focusing ontheir intricate interplay in AD. Wehypothesizethat impaired mitophagy in AD disrupts intracellular redox and iron homeostasis, thereby increasing neuronal susceptibility to ferroptosis. Conversely, ferroptosis-associated events, such as lipid peroxidation, can further exacerbate mitochondrial dysfunction,thereby establishing a vicious cycle that accelerates disease progression. Furthermore, we summarize potential therapeutic strategies targeting this interactive network (e.g.,Urolithin A, ferroptosis inhibitors) anddiscusspromising future research directions. A deeper understanding of the crosstalk between mitophagy and ferroptosis is therefore crucial for developing novel therapeutic interventions for AD.
Ask to review this manuscript

Notes for potential reviewers

  • Volunteering is not a guarantee that you will be asked to review. There are many reasons: reviewers must be qualified, there should be no conflicts of interest, a minimum of two reviewers have already accepted an invitation, etc.
  • This is NOT OPEN peer review. The review is single-blind, and all recommendations are sent privately to the Academic Editor handling the manuscript. All reviews are published and reviewers can choose to sign their reviews.
  • What happens after volunteering? It may be a few days before you receive an invitation to review with further instructions. You will need to accept the invitation to then become an official referee for the manuscript. If you do not receive an invitation it is for one of many possible reasons as noted above.
  • PeerJ does not judge submissions based on subjective measures such as novelty, impact or degree of advance. Effectively, reviewers are asked to comment on whether or not the submission is scientifically and technically sound and therefore deserves to join the scientific literature. Our Peer Review criteria can be found on the "Editorial Criteria" page - reviewers are specifically asked to comment on 3 broad areas: "Basic Reporting", "Experimental Design" and "Validity of the Findings".
  • Reviewers are expected to comment in a timely, professional, and constructive manner.
  • Until the article is published, reviewers must regard all information relating to the submission as strictly confidential.
  • When submitting a review, reviewers are given the option to "sign" their review (i.e. to associate their name with their comments). Otherwise, all review comments remain anonymous.
  • All reviews of published articles are published. This includes manuscript files, peer review comments, author rebuttals and revised materials.
  • Each time a decision is made by the Academic Editor, each reviewer will receive a copy of the Decision Letter (which will include the comments of all reviewers).

If you have any questions about submitting your review, please email us at [email protected].