Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.

Small molecular therapeutic targets for neurodegenerative diseases.

A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.

Genetic and physiological basis of Alzheimer’s disease: A review

Alzheimer's disease (AD) is the primary cause of dementia globally and the most prevalent neurodegenerative disease. Progressive memory loss, cognitive impairment, behavioral abnormalities, and loss of functional independence are its hallmarks. The development of Alzheimer’s disease is strongly associated with both genetic predisposition and physiological dysfunctions within the central nervous system. Modern scientific advances have revealed that multiple genes, including APOE, APP, PSEN1, and PSEN2, contribute to disease susceptibility and progression. Furthermore, the disease's key clinical features include physiological anomalies such amyloid-beta buildup, tau hyper-phosphorylation, neuro-inflammation, oxidative stress, mitochondrial dysfunction, and synaptic degeneration. Additionally, recent research highlights the importance of cellular senescence, non-coding RNAs, and epigenetics in the pathophysiology of AD. Understanding the relationship between genetics and physiology provides new opportunities for early diagnosis and targeted therapeutic interventions. This article reviews the current understanding of the genetic and physiological mechanisms underlying Alzheimer’s disease and discusses modern approaches for diagnosis and treatment.

Genetic and epigenetic complexity of Parkinson's disease: From dopamine pathways to estrogen interplay.

Emerging Advances in Neuropharmacology: Novel Therapeutic Targets for Neurodegenerative Disorders

Neurodegenerative diseases are a heterogeneous group of chronic and progressive disorders, which are characterized by selective neuronal destruction, synaptic malfunction and progressive cognitive and locomotor dysfunction. The major ones are Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis which are a formidable and growing global health and socio-economic burden mainly due to demographic aging. Even despite the advances in the symptomatic treatment, predominantly through the cholinergic, dopaminergic, glutamatergic, and GABAergic system, the current treatment regimens are not able to stop the underlying neurodegenerative events or reverse them. There is mounting evidence that convergent pathogenic mechanisms, such as protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, impaired autophagy-lysosomal pathways, synaptic dysfunction, and chronic neuroinflammation, are convergent mechanisms. These convergent molecular and cellular cascades provide a strong rationale behind the identification of new neuropharmacological targets, which include: kinases, phosphatases, epigenetic regulators, neurotrophic signalling pathways and neuroimmune mediators. Advances in the biomarker discovery, genomics and systems biology have further enabled the use of precision based therapeutic stratification and early-intervention approaches. Genetic, nanotechnology, and RNA-based therapeutics as well as biologics are reconfiguring translational models in neurodegeneration. A mechanism-based, multi-target, precision neuropharmacological approach, as a group, has significant potential in achieving long-term neuroprotection, improved clinical and disease modification in neurodegenerative diseases.

Neuroinflammatory and molecular pathways in Alzheimer's disease: mechanistic crosstalk and emerging therapeutic opportunities.

Overall, this review makes a case for integrative, pathway-based therapeutic models, and multiple approaches may facilitate for drug development, biomarker identification and patient management in Alzheimer's disease.

Decoding the Genetic Basis of Alzheimer's Disease: A Comprehensive Review of Key Causal and Risk Genes, Pathological Mechanisms, Convergent Pathways, and Emerging Therapeutic Targets

Alzheimer's disease (AD) is the leading cause of dementia worldwide, accounting for approximately 60–70% of all dementia cases. It is a progressive neurodegenerative disorder that results in memory loss, cognitive decline and functional impairment, and affects over 55 million individuals worldwide. The number of affected individuals is projected to reach 139 million by 2050, posing a substantial public health and socioeconomic burden. Pathologically, AD is defined by extracellular deposits of amyloid-β (Aβ) plaques and intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles (NFTs). There is growing evidence that the pathogenesis of AD is multifactorial, involving genetic, molecular, and environmental factors. This review aims to give a comprehensive overview of the major genes and molecular pathways involved in the pathogenesis of AD, as well as recent advances in genome-wide association studies (GWAS) and emerging therapeutic strategies. The mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1), presenilin 2 (PSEN2), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) are associated with early-onset familial AD, while late-onset AD is linked to several susceptibility genes identified by GWAS. The molecular mechanisms underlying AD pathogenesis and progression are discussed with respect to major AD-associated genes, such as microtubule-associated protein tau (MAPT), apolipoprotein E (APOE), triggering receptor expressed on myeloid cells 2 (TREM2), sortilin-related receptor 1 (SORL1), bridging integrator 1 (BIN1), phosphatidylinositol-binding clathrin assembly protein (PICALM), Clusterin (CLU), ATP-binding cassette subfamily A member 7 (ABCA7), complement receptor 1 (CR1), acetylcholinesterase (AChE), nuclear factor erythroid 2-related factor 2 (NRF2), and tumor necrosis factor (TNF). Current therapeutic strategies, including anti-amyloid immunotherapy, AChE inhibitors, tau-directed therapies, and emerging gene-targeted approaches, are also discussed. In addition, progress in multi-omics technologies, disease models using induced pluripotent stem cells (iPSC), gene editing with CRISPR-Cas9, and artificial intelligence (AI) analysis are likely to speed up the implementation of precision medicine for early diagnosis, risk prediction, and treatment of Alzheimer's disease.