Protective Effect of Antioxidants on Neuronal Dysfunction and Plasticity in Huntington’s Disease

Abstract

Huntington's disease (HD) is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain. The process of adult neurogenesis has been implicated in the cognitive functions of the brain and is highly modulated positively by different factors including antioxidants. The supportive role of antioxidants to reduce the severity of HD via promoting the functional neurogenesis and neuroprotection in the pathological adult brain has great promise. This review comprehends the recent studies describing the therapeutic roles of antioxidants in HD and other neurologic disorders and highlights the scope of using antioxidants to promote adult neurogenesis in HD. It also advocates a new line of research to delineate the mechanisms by which antioxidants promote adult neurogenesis in HD.

Customized Dietary Intervention Avoids Unintentional Weight Loss and Modulates Circulating miRNAs Footprint in Huntington's Disease

“…Overall, preintervention, detailed interviews elaborated by the nutritionist (Appendix 2, Supporting Information) revealed that patients had a low‐to‐moderate intake of macronutrients, thus coinciding with a 1989 study that reported a low fat and carbohydrates intake in HD‐patients . After an exhaustive review of guidelines and literature, the nutritionist followed the recommendation of 25–35 kcal kg –1 d –1 , deciding against the high calorie intake frequently recommended (3500–5000 kcal d –1 ), and including essential bioactive compounds . On that basis, a customized diet was designed for each participant, and adherence to these recommendations was high, with the exception of participant number 11, who was diagnosed with anorexia nervosa.…”

“…In HD, it was reported that antioxidants may exert beneficial effects, promoting the functional neurogenesis. Specifically, dietary polyphenols ameliorated anxiety and depression via regulation of adult hippocampal neurogenesis, while flavanoids protected hippocampal neurons from oxidative stress …”

Towards a comprehensive understanding of the contributions of mitochondrial dysfunction and oxidative stress in the pathogenesis and pathophysiology of Huntington's disease

“…Several lines of evidence indicate that OS plays a critical role in psychiatric disorders (Hassan et al, ; Moniczewski et al, ; Ng, Berk, Dean, & Bush, ; Salim, ; Smaga et al, ; Tsaluchidu, Cocchi, Tonello, & Puri, ). Indeed, OS contributes to impaired adult hippocampal neurogenesis in HD (Velusamy et al, ) and antioxidants have been proposed to promote adult neurogenesis in HD (Velusamy et al, ).…”

Biophysical interaction of resveratrol with sirtuin pathway Significance in Alzheimer rsquo s disease

“…Anti-inflammatory action of RSV has shown to prevent lipopolysaccharide (LPS, a TLR4 ligand)-induced activation of murine RAW 264.7 macrophages and microglial BV-2 cells. RSV treatment has been reported to prevent pro-inflammatory effect of Aβ on macrophages by inhibiting activation of STAT1, STAT3 and NFκB activation by interfering with IKK and IκB phosphorylation (78). In addition, oral administration of RSV in a mouse model of cerebral amyloid deposition significantly reduced microglial activation related to amyloid deposition.…”