Back to all available

Deciphering the modulatory role of short-chain fatty acids in Parkinson’s disease through phosphorylation-dependent signaling mechanisms

biochemistry
neuroscience
cognitive-disorders
neurology
metabolic-sciences

Abstract

Parkinson’s disease (PD), the world’s second most prevalent neurodegenerative disorder, is characterized by progressive neuronal degeneration driven by complex pathological mechanisms. Phosphorylation signaling pathways have increasingly been recognized as critical modulators in PD development and progression. Meanwhile, short-chain fatty acids (SCFAs), primarily produced by gut microbiota, have demonstrated notable neuroprotective potential by promoting autophagy, alleviating mitochondrial dysfunction, and regulating neuroinflammatory responses. Emerging research suggests that SCFAs may influence the phosphorylation dynamics of key signaling pathways—including MAPKs, NF-κB, JAK/STAT, PI3K/Akt, AMPK, and Nrf2/Keap1/ARE—thereby modulating PD pathophysiology.

This review aims to systematically evaluate existing evidence on the interplay between SCFAs and these phosphorylation cascades, elucidating their roles in PD pathogenesis.

In addition to synthesizing current findings, this review proposes novel mechanistic hypotheses and outlines future research directions that may facilitate the identification of new molecular targets, offering valuable insights into therapeutic strategies and preventive interventions for PD.

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].