MITOPHAGY AND MEMORY: CAN A NATURAL COMPOUND FROM POMEGRANATES COMBAT ALZHEIMER’S DISEASE ?

Alzheimer's disease is a progressive neurodegenerative disorder that predominantly impacts the brain, leading to a gradual decline in memory, thinking, and cognitive abilities. It affects over 10 % of adults aged 65 and older, with its prevalence expected to triple globally by 2050. Alzheimer's disease is characterized by cognitive decline and behavioral changes. Pathological features include Amyloid plaques from Amyloid beta (Aβ) and neurofibrillary tangles. Ageing is a substantial risk factor, and impaired autophagy, DNA damage, neuroinflammation, cellular decline, and mitochondrial dysfunction all contribute to disease progression.

Mitophagy is the removal of damaged mitochondria which is essential for brain health. Mitophagy has been demonstrated to be defective in Alzheimer's disease patients and models. Inducing mitophagy using genetic techniques or chemicals improves cognitive functioning and reduces Aβ plaques.

Possible preventive effects of the compound Urolithin A

Urolithin A (UA) is a promising natural molecule created by gut bacteria that breaks down ellagitannins and ellagic acid, which are present in pomegranates, berries, and nuts. UA has been researched for its effects on aging and disease. It promotes cellular health by boosting mitophagy, improving mitochondrial function, and decreasing inflammation. Short-term UA therapy in Alzheimer's disease models improved learning and memory. UA also stimulates the expression of mitophagy-related genes, implying that it has potential in Alzheimer's disease therapy.

Mechanism of action of compound Urolithin A

UA's mechanisms include reducing oxidative stress, removing Aβ from neurons, and inhibiting cancer cell proliferation regulators. Although primarily studied for mitochondrial and muscle health in humans, UA crosses the blood-brain barrier, indicating its potential therapeutic role in the brain. Given the low success rate of AD therapy development, focusing on core features of AD pathogenesis, such as faulty mitophagy, shows promise. Aging is the most significant risk factor for Alzheimer's disease, and UA tackles a variety of aging and AD deficits. Extended UA treatment adds to its potential utility against AD.

 

Reference:

Hou, Yujun, Xixia Chu, Jae‐Hyeon Park, Qing Zhu, Mansoor Hussain, Zhiquan Li, Helena Borland Madsen, et al. "Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions." Alzheimer's & Dementia (2024).

Image Source:

1.Cover image: https://healthnews.com/nutrition/vitamins-and-supplements/best-urolithin-a-supplement/

2. Alzheimer's & Dementia: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13847