Targeting the molecular web of Alzheimer’s disease: unveiling pathways for effective pharmacotherapy

Abstract

Introduction Alzheimer’s disease is a neurocognitive disorder that affects elderly people by slowly impaired cognition, dementia, and gets worse with age. It slowly impacts the quality of life. Clinically, it is distinguished by a transition from episodic memory to a gradual reduction in cognitive ability leading to cognitive dysfunction. Neurofibrillary tangles and amyloid plaques are unique structures that are thought to have a role in the pathogenesis of Alzheimer's disease. In this review, we focus our attention on the risk factors, pathophysiology, etiology, epidemiology, stages, diagnosis, treatment, mechanisms, pathways, ongoing clinical trials data and risks potentially associated with the development of Alzheimer's disease. Short summary This review aims to extrapolate the information about Alzheimer's disease. Preliminary research was done by selecting reviews on PubMed, Elsevier, and Google open-access publications using the keywords like “Alzheimer, dementia, neurodegenerative, memory, amyloid β, mechanism of action, pathways”. Conclusion Here we show the discussion and interpretation of several signaling pathways in the pathogenesis of Alzheimer's disease such as amyloid β plaque cleavage, Metal ion hypothesis, amyloid β degradation, initiation of amyloidogenic and non-amyloidogenic pathway, oxidative stress hypothesis, Metabolic syndrome, insulin resistance and tau phosphorylation associated apolipoprotein- cholesterol, neurofibrillary tangles accumulation, and insulin resistance which are significant for better understanding of the disease initiation and progression. On studying the ongoing clinical trials, it was found that current drugs being tested are crenezumab, gantenerumab and sodium oligonucleotide. Graphical Abstract

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

“…The gender-specific effect was found, whereby the interaction between COMT and APOE was more prominent in female individuals who have been diagnosed with AD (Reynolds et al, 1999). On the other hand, the male population with MCI demonstrated the greatest level of synergy between the aforementioned pair of genes (Jadhav et al, 2024). Another study reported a correlation between COMT rs4680 alleles and sporadic AD in males (Dunk et al, 2023).…”

“…The identification of pharmacological interventions that target ERα is considered a critical element in the preservation of neuronal function and the prevention of neurodegeneration (Wang et al, 2024). The neuroprotective properties of E2 and SERMs, namely, tamoxifen and raloxifene, have been documented in human neuronal cells (Jadhav et al, 2024). The aforementioned compounds have demonstrated an ability to enhance resistance against the toxic effects induced by Aβ (Plascencia-Villa & Perry, 2020).…”

Comprehensive Overview of Alzheimer’s Disease: Etiological Insights and Degradation Strategies

“…Some of these include Gosuranemab, Tilavonemab, Semorinemab, Zagotenemab, Aducanumab [210], Lecanemab [211], and anti-tau antibodies, which have shown significant improvement in patients at early stages [20]. However, vaccines targeting the tau protein, such as the anti-tau vaccine (AADvac1) and ACI-35, are yet to demonstrate thera-peutic outcomes [212,213]. Additionally, pharmacological treatments such as donepezil, galantamine, rivastigmine, and memantine are currently available drugs that mostly inhibit acetylcholinesterase and activate NMDA receptors, offering symptomatic relief in AD [20,212,214].…”