title: Neuroprotective mechanisms of peroxisome proliferator-activated receptor agonists in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common causes of dementia accounting for 50-60% of all cases. The pathological hallmarks of AD are the formation of extracellular plaques consisting of amyloid-β protein, intracellular neurofibrillary tangles of hyperphosphorylated tau proteins and presence of chronic neuroinflammation causing progressive decline in memory and cognitive functions. The current therapeutic strategies to improve memory deficits aim at preventing the formation and accumulation of amyloid-β and tau phosphorylation. Beyond the plaque and tangle-related targets, other aspects of pathophysiology including molecular transport mechanism, oxidative damage, inflammation and glucose and lipid metabolism may also provide opportunities to slow down the progression of memory loss. A novel therapeutic approach to the treatment of AD is through the exploration of nuclear receptor agonists, peroxisome proliferator-activated receptors (PPARs), which have been clinically used as antidiabetic and dyslipidemic agents. The findings that PPAR agonists may possess antiamyloidogenic, anti-inflammatory, insulin-sensitizing, and cholesterol-lowering potential suggest that they could be interesting candidates for AD drugs. Through this review, we will discuss the probable pathophysiological mechanisms that may elicit the defending role of these receptors in brains of AD patients.
authors: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
authors: Rupinder K
authors: RK
authors: Sodhi
authors: Nirmal
authors: N
authors: Singh
authors: Amteshwar S
authors: AS
authors: Jaggi
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