Affiliation:
1. Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
Abstract
Abstract:
Alzheimer's disease (AD) is the most common form of dementia, having characteristic clinical
features of progressive memory loss and visuospatial, language, and cognitive impairment. In addition,
patients often suffer from comorbid depression and aggression. Aging is a major contributing
factor, though the exact pathophysiological involvement in the disease progression is debatable. Biologists
demonstrate that AD is not a result of a single pathological incident. However, an uncontrolled
myriad of events is responsible for the pathophysiological condition; hence, it is regarded as a multifaceted
disease. Pathophysiologically, AD is described by having a long preclinical stage (proteinopathy
accumulation stage), followed by a short prodromal/dementia stage (clinical symptom onset), as
evident via biomarker studies. Specific and sensitive biomarkers are needed to track disease progression
and treatment. Neuroinflammation is one of the cardinal pathophysiological events of AD that
form a positive activation loop between proteinopathy and pro-inflammatory mediators. However, the
starting point is inconclusive. The vital cells, like glia, known as brain scavenger cells, remain in harmony
between their quiescent and activated morphological states during any stimulus and help to regulate
the neuroinflammatory microenvironment. Hence, focusing on the dysfunctional microglia could
be a novel therapeutic approach to managing neuroinflammation condition in AD. This review focuses
on the translational evidence of anti-diabetic and anti-inflammatory candidates in AD management.
It also highlights the importance of the microglia activation spectrum, eicosanoid signaling, cytokine
signaling, and inflammatory mediators responsible for the neuroinflammation cascade. The repeated
failure of single-approached therapies has diverted researchers’ attention to AD-modifying approaches
and AD multimodal treatment plans. This review is an effort to brief the role of new players (like micronutrients
and nutraceutical applications) that have been reported as helpful in suppressing AD severity.
Apart from anti-diabetic candidates, various insulin-mimetic and insulin-sensitizer drugs have
also been assessed to target insulin insensitivity to mitigate AD progression. However, these possibilities
are in the investigational stage and not clinically established yet, though various AD animal models
have verified the positive outcome.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology,General Medicine
Cited by
5 articles.
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