Genetics of Parkinson Disease and Related Disorders: Mechanisms and Therapeutic Prospects

Genetic research in Parkinson disease (PD) and related disorders has advanced significantly in recent years, primarily through large-scale genome-wide association studies (GWAS) and the identification of mutations in genes such as GBA, LRRK2, and SNCA (synuclein). Despite these advances, clinicians and researchers still face challenges in linking specific genotypes to distinct clinical phenotypes, and debate persists regarding the precise roles and interplay of identified genetic risk factors. Recent studies have shed light on the molecular mechanisms underpinning disease onset and progression, highlighting both inherited and sporadic components, yet major gaps remain in understanding how these insights can be effectively translated into precision medicine. While novel interventions—including autophagy promoters, kinase inhibitors, synuclein-directed antibody therapies, and vaccinations—are at various stages of clinical translation, comprehensive evaluations of their underlying genetic rationales and potential for disease modification are still needed.This Research Topic aims to provide a thorough exploration of the genetic mechanisms underlying PD and related disorders, and to critically review emerging and established therapeutic strategies that target these mechanisms. We seek to clarify which genetic abnormalities most significantly contribute to disease pathogenesis and phenotype variation, to examine how advances in gene therapy and related interventions might reshape therapeutic strategies, and to foster new hypotheses and approaches for disease modification. Special attention will be given to genotype-phenotype correlations and the translation of genetic discoveries into clinical interventions.Our focus will be on the interface between gene-based pathogenesis and therapy in PD and related disorders, while limiting the scope to genetic factors with established or emerging clinical relevance and their associated therapeutic approaches. To gather further insights in these boundaries, we welcome articles addressing, but not limited to, the following themes:-Critical reviews of GBA, LRRK2, synuclein, and other well-documented PD-related genes-Genotype-phenotype relationships and their implications for diagnosis and prognosis-Advances in gene therapy and genetic-based interventions for PD-Disease-modifying strategies: autophagy modulation, kinase inhibition, and immunotherapies-Molecular and cellular mechanisms linking genetic mutations to neurodegeneration-Challenges and future perspectives in translating genetic discoveries into clinical care Topic editors: TAKAHASHI MAKIO, Nobutaka Hattori Source: https://www.frontiersin.org/research-topics/79753/genetics-of-parkinson-disease-and-related-disorders-mechanisms-and-therapeutic-prospects