Therapeutic insights elaborating the potential of retinoids in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is perceived with various pathophysiological characteristics such oxidative stress, senile plaques, neuroinflammation, altered neurotransmission immunological changes, neurodegenerative pathways, and age-linked alterations. A great deal of studies even now are carried out for comprehensive understanding of pathological processes of AD, though many agents are in clinical trials for the treatment of AD. Retinoids and retinoic acid receptors (RARs) are pertinent to such attributes of the disease. Retinoids support the proper functioning of the immunological pathways, and are very potent immunomodulators. The nervous system relies heavily on retinoic acid signaling. The disruption of retinoid signaling relates to several pathogenic mechanisms in the normal brain. Retinoids play critical functions in the neuronal organization, differentiation, and axonal growth in the normal functioning of the brain. Disturbed retinoic acid signaling causes inflammatory responses, mitochondrial impairment, oxidative stress, and neurodegeneration, leading to Alzheimer’s disease (AD) progression. Retinoids interfere with the production and release of neuroinflammatory chemokines and cytokines which are located to be activated in the pathogenesis of AD. Also, stimulating nuclear retinoid receptors reduces amyloid aggregation, lowers neurodegeneration, and thus restricts Alzheimer’s disease progression in preclinical studies. We outlined the physiology of retinoids in this review, focusing on their possible neuroprotective actions, which will aid in elucidating the critical function of such receptors in AD pathogenesis.

Epigallocatechin Gallate Ameliorates Nicotine Withdrawal Conditions-Induced Somatic and Affective Behavior Changes in Mice and Its Molecular Mechanism

“…The pathophysiological pathway involved changes in neurotrophic support and neuron–glia interaction, resulting in central sensitization to pain, which was linked to the same pathway in depressive and anxiety symptoms [ 34 , 39 ]. Glucocorticosteroids in the brain played an important physiological process involved in various stress-related conditions to preserve neuroplasticity within the hippocampus [ 40 ]. Research had established that the neurohormonal stress axis involving sympathoadrenal, and HPA activation played a crucial role in the onset and progression of alcoholic neuropathy [ 41 ].…”

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

“…Alzheimer's disease (AD) is a type of irreversible neurological disorder that is mainly identified among elderly people globally. Statistically, a staggering 15 million people suffer from AD worldwide, making it the most prevalent neurological condition in the world [ 1 ]. The steady increase in AD cases is partly attributed to the aging global population.…”

“…Researchers have revealed that aberrant Aβ and tau proteins may play a significant role in AD pathogenesis. Generally, it is understood that the amyloid hypothesis of AD describes the neurodegeneration and memory deficits in AD patients due to the buildup of the Aβ plaque in the temporal lobe [ 1 ]. Consequently, these aggregates trigger numerous effects, including mitochondrial dysfunction, neuroinflammation, oxidative stress, and calcium imbalances, resulting in the loss of white matter in the brain and neurons.…”

Genetic influences on circulating retinol and its relationship to human health

“…Synthetic retinoids that are structurally similar to retinol/retinoic acid are approved for dermatological indications (e.g., adapalene) and some cancers (e.g., bexarotene) 10 , 11 , as well endogenous retinoids including all- trans retinoic acid (tretinoin) and 13- cis retinoic acid (isotretinoin) used in dermatology. There is also continued interest in repurposing both endogenous and synthetic retinoids across a range of other indications, including neuropsychiatry 2 , 12 . Currently, retinol supplementation is not specifically indicated unless an individual is deficient, which is rare in high-income countries, though much more common in low-income countries.…”

“…Numerous observational or randomised controlled studies have explored the effects of supplementation, a high vitamin A diet, and/or measured circulating retinol in a variety of disease contexts. However, the data from these efforts have often either been null or conflicting between studies 12 – 16 . Despite this, recent observational evidence suggests a relationship between a greater circulating retinol abundance and lower mortality in a large, prospective 30-year follow-up study 17 .…”