Mitochondrial dysfunction and disrupted neuronal lipid homeostasis in Parkinson's disease: Potential mechanisms and therapeutic implications.

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

BackgroundParkinson's disease (PD) is a multifactorial neurodegenerative disorder characterised by dopaminergic neuron loss and pathological accumulation of alpha-synuclein. Emerging evidence highlights a crucial interplay between mitochondrial dysfunction and disrupted lipid homeostasis as central mechanisms driving PD pathogenesis.ObjectiveThis scoping review synthesises current evidence on the relationship between mitochondrial dysfunction and neuronal lipid dysregulation in PD and identifies potential therapeutic targets within these intersecting pathways.MethodsFollowing the PRISMA-ScR guidelines, a comprehensive literature search was conducted across PubMed, Embase, and Web of Science for studies published between 2015 and 2025. Two independent reviewers screened and selected eligible studies based on predefined inclusion criteria.ResultsAnalysis revealed four central interconnected pathological mechanisms: ferroptosis, alpha-synuclein-lipid interactions, mitochondrial dysfunction, and impaired autophagy/mitophagy. These mechanisms collectively contribute to oxidative stress, membrane destabilisation, and bioenergetic collapse, driving dopaminergic neuronal vulnerability.ConclusionsThe findings underscore a complex, bidirectional relationship between mitochondrial dysfunction and lipid dysregulation in PD. Therapeutic strategies targeting iron accumulation, lipid peroxidation, and alpha-synuclein aggregation are promising. However, further mechanistic studies are required to clarify these interactions and advance the development of effective disease-modifying interventions.

Related topics