Principal Investigators


BOHR, VILHELM A

Institution


National Institute on Aging

Contact information of lead PI


Country


USA

Title of project or programme


Mitophagy upregulation as a therapeutic strategy for Alzheimers disease

Source of funding information


NIH (NIA)

Total sum awarded (Euro)


122853.211

Start date of award


Total duration of award in years


1

Keywords


Acquired Cognitive Impairment... Aging... Alzheimer's Disease... Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)... Brain Disorders... Dementia... Health Disparities for IC Use... Neurodegenerative... Neurosciences

Research Abstract


We seek to explore the relationship between mitochondrial dysfunction and accumulation of damaged mitochondria in AD. We have established C. elegans models to investigate whether mitophagy contributes to AD pathology. We have detected mitochondrial quality in wild type (N2) and hu-Tau or Abeta-overexpressed AD C. elegans models (RB809/ptl-1 (ok621); BR5270 (byIs161); CL2120 (dvIs14); CL2355) using confocal microscopy, electron microscopy, and Seahorse respirometry. All the AD worms showed accumulation of damaged mitochondria, impaired mitochondrial network, and decreased basal oxygen consumption. We propose that defective mitophagy contributes to accumulation of damaged mitochondria in AD. Mitophagy will be evaluated using multiple techniques such as immunoblotting for protein expression, a mitophagy reporter worm strain, mitophagy dyes, and the mt-mKeima reporter. Our preliminary data indicate defective mitophagy in Tau and Abeta overexpressing cells. In the future, we apply therapeutic strategies to modulate mitophagy and offset AD mitochondrial phenotypes. We will investigate whether mitophagy induction can improve healthspan endpoints (swimming movement; pharyngeal pumping; maximum velocity), and extend lifespan of AD worms models.

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