2026· Advances in Protein Chemistry and Structural Biology· Vol 153, pp.
135-167
· 0 citations
Medicine
TL;DR
A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.
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.
This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT.
P. Pattnaik, S. Prusty, Sanghamitra Pati et al.· Gene· 0 citations
Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.
A. Domínguez-García, J. C. Delgado-Uriarte, A. Cervantes-Arriaga· Revista de investigacion cli...· 0 citations
Natural bioactive compounds, gene-based therapies, stem cell-based therapies, stem cell-based therapies, and nanotechnology-assisted drug delivery systems are promising alternatives as suggested by recent advances and could help to more effectively and permanently manage PD.
S. Arbab, Hanif Ullah, Yanting Han et al.· Ageing Research Reviews· 0 citations
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.
Recent advances in multitarget drug development for AD and PD targeting compounds targeting Aβ, BACE1, MAO-B, cholinesterases, metal-ion dyshomeostasis, oxidative stress, and inflammatory pathways are reviewed.
Azmatullah Khan, Abdullah Abdullah, Syeda Farwa Naqvi et al.· Zeitschrift für Naturforschu...· 0 citations
