A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation

Abstract

SIRT3, the primary mitochondrial deacetylase, regulates the functions of mitochondrial proteins including metabolic enzymes and respiratory chain components. Although SIRT3’s functions in peripheral tissues are well established, the significance of its downregulation in neurodegenerative diseases is beginning to emerge. SIRT3 plays a key role in brain energy metabolism and provides substrate flexibility to neurons. It also facilitates metabolic coupling between fuel substrate-producing tissues and fuel-consuming tissues. SIRT3 mediates the health benefits of lifestyle-based modifications such as calorie restriction and exercise. SIRT3 deficiency is associated with metabolic syndrome (MetS), a precondition for diseases including obesity, diabetes, and cardiovascular disease. The pure form of Alzheimer’s disease (AD) is rare, and it has been reported to coexist with these diseases in aging populations. SIRT3 downregulation leads to mitochondrial dysfunction, neuroinflammation, and inflammation, potentially triggering factors of AD pathogenesis. Recent studies have also suggested that SIRT3 may act through multiple pathways to reduce plaque formation in the AD brain. In this review, we give an overview of SIRT3’s roles in brain physiology and pathology and discuss several activators of SIRT3 that can be considered potential therapeutic agents for the treatment of dementia.

Pectolinarigenin Improves Oxidative Stress and Apoptosis in Mouse NSC-34 Motor Neuron Cell Lines Induced by C9-ALS-Associated Proline–Arginine Dipeptide Repeat Proteins by Enhancing Mitochondrial Fusion Mediated via the SIRT3/OPA1 Axis

“…It can prevent or alleviate mitochondrial dysfunction and has neuroprotective effects [31]. Modulation of SIRT3 activity now represents a powerful strategy for treating neurodegenerative diseases [55]. A previous study showed that increasing NAD + levels upregulates SIRT3 activity [56].…”

Effect of Nutrients and Phytochemical Compounds of <i>Solanum melongena</i> (Eggplants) on Cognitive Protection in Rats

“…Neurodegenerative diseases occur with ageing and many elderly people are more and more exposed. It affects the neurology system, then conducts to brain cell death [1]. The main symptoms are characterized by loss of autonomy, depression, anxiety, progressive memory loss, language disability, bradykinesia and muscular rigidity… [2].…”

Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/β‐catenin cascade inactivation

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