Epigenetic modulators as therapeutics for neurodegenerative disorders/Alzheimer's disease.

The potential of HDAC inhibitors for Alzheimer's disease.

Histone deacetylase as a potential therapeutic target for memory dysfunction during aging and neurodegenerative disorders.

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.

Biochemical modulators of synaptic plasticity: New horizons in Alzheimer's disease treatment.

Synaptic dysfunction is the earliest and most critical pathological feature of Alzheimer's disease (AD), directly contributing to cognitive decline. This review provides an integrative overview of the molecular and biochemical modulators governing synaptic plasticity and their disruption in AD. We discuss how the collective impairment of Aβ aggregation, tau pathology, calcium imbalance, oxidative stress, and neuroinflammation affects dendritic spine morphology and synaptic connectivity. Particular attention is given to neurotrophins such as brain-derived neurotrophic factor and TrkB signaling, hormonal influences, likewise glucocorticoids, estrogens, testosterone, endocannabinoid pathways, lipid and cholesterol regulators like ApoE and lipid rafts, and epigenetic mechanisms that modulate synaptic resilience. We further evaluate the therapeutic potential of pharmacological agents, including cholinesterase inhibitors, NMDA receptor modulators, and multi-target directed ligands alongside nutraceuticals such as resveratrol, curcumin, omega-3 fatty acids, Withania somnifera, and Bacopa monnieri. Emerging technologies, including iPSC-derived neuronal models, optogenetics, and advanced neuroimaging biomarkers like SV2A PET, cerebrospinal fluid/plasma neurogranin, are also highlighted for their role in elucidating and monitoring synaptic integrity. Ultimately, targeting the biochemical modulators of synaptic plasticity offers a promising avenue for AD therapy, especially through combinatorial and precision-medicine strategies aimed at restoring synaptic function and cognitive performance.

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.

Epigenetic Regulation in Parkinson’s Disease: Cutting -Edge Insights into miRNAs, lncRNAs and Chromatin Modifiers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal aggregation of α-synuclein. While genetic mutations contribute to disease susceptibility, accumulating evidence highlights the pivotal role of epigenetic regulation in modulating gene expression and disease progression. The epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA-mediated regulation, dynamically influence neuronal function, neuroinflammation, mitochondrial homeostasis, and protein aggregation in Parkinson’s disease. Recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are critical regulators of α-synuclein expression, dopaminergic neuron survival, and inflammatory signaling pathways. In parallel, chromatin modifiers such as histone acetyltransferases and deacetylases orchestrate transcriptional programs that determine neuronal vulnerability and resilience. The intricate crosstalk among miRNAs, lncRNAs, and chromatin-modifying complexes underscores the complexity of epigenetic networks in PD pathogenesis. Furthermore, epigenetic alterations have emerged as promising biomarkers for early diagnosis and disease monitoring, as well as attractive therapeutic targets for disease-modifying interventions. Advances in epigenetic-based therapies, including histone deacetylase inhibitors and RNA-based strategies, offer new opportunities for precision medicine in Parkinson’s disease. This review critically summarizes current insights into the roles of miRNAs, lncRNAs, and chromatin modifiers in Parkinson’s disease, discusses their potential as biomarkers and therapeutic targets, and highlights key challenges and future perspectives in translating epigenetic discoveries into clinical applications.