Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), are defined by distinct pathological changes in specific brain regions and the gradual loss of neurons. Although extensive research has been conducted over the past several decades, the mechanisms that drive neuronal cell death remain incompletely understood, and no definitive treatments are currently available. Clarifying these mechanisms is of paramount importance for identifying novel therapeutic strategies.
Neurons demand a considerable amount of energy, primarily in the form of ATP generated through oxidative phosphorylation (OXPHOS). Mitochondrial dysfunction in this pathway is a prominent feature in both AD and PD, leading to inadequate ATP production, compromised energy homeostasis, and excessive accumulation of reactive oxygen species.
This project will use UK Biobank data to identify single nucleotide polymorphisms (SNPs) and other genetic variations related to mitochondrial OXPHOS. Potential associations with neurodegeneration will be explored. The variants of interest will then be replicated in induced pluripotent stem cells (iPSCs) via CRISPR-Cas9 genome editing, followed by differentiation into neurons. By examining the functional impact of these alterations, this study may further elucidate the molecular basis of AD and PD, ultimately guiding the development of new biomarkers and therapeutic interventions.
Using the data from the UK Biobank and the analysis results, I plan to disseminate my findings through presentations at the International Society for Stem Cell Research (ISSCR) annual meeting, as well as through preprint publication on bioRxiv and submission to peer-reviewed journals.
My goal is to share these findings widely to contribute to scientific progress and, ultimately, to help improve the lives of patients suffering from neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.
