Jul 2026· Ageing Research Reviews· pp.
103263
· 0 citations· 258 references
Medicine
TL;DR
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.
Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. It is associated with the ongoing degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies that contain α-synuclein. These pathological changes lead to abnormalities of motor symptoms (tremor, rigidity, bradykinesia) and non-motor symptoms (cognitive decline, sleep abnormalities, psychiatric abnormalities). The pathogenesis of PD is complex and multifactorial, involving interconnected mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy, ferroptosis, and genetic factors. To develop effective therapeutic interventions, these pathways need to be understood. Current treatments, such as levodopa and deep-brain stimulation (DBS), are symptom-based and do not break disease progression. Thus, considerable research efforts have been geared towards finding disease-modifying therapeutic strategies. Natural bioactive compounds, gene-based therapies, stem cell-based therapies, and nanotechnology-assisted drug delivery systems are promising alternatives as suggested by recent advances. Antioxidant compounds like curcumin, resveratrol, and epigallocatechin gallate (EGCG) show promising antioxidant and neuroprotective effects, and nanomedicine provides boosted delivery to the brain and targeted drug distribution. In future clinical applications, these new strategies could help to more effectively and permanently manage PD.
This review focuses on the potential molecular mechanism underlying KLF4-mediated neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis and targeting them appears to be a viable therapeutic strategy for treating PD.
Anjali Kumari, K. Aran· Current Medical Science· 0 citations
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.
New knowledge about the protective and detrimental aspects of neuroinflammation in AD and PD is summarized, providing an analysis on these developing prospects for targeted interventions toward slowing or stopping neurodegeneration.
R. Kumar, Kamaljeet, Sourabh Kosey· InflammoPharmacology· 0 citations
Overall, saponins represent a promising avenue for the development of novel neuroprotective and disease-modifying therapies for PD, and challenges such as poor bioavailability in natural sources and limited access to brain remain significant barriers to clinical translation.
Debasmita Tripathy, Shreya Sen Sarma, Deepak Kumar et al.· Neurochemistry International· 0 citations
This work incorporates disease-specific mitochondrial pathology with current progress in targeted nanotherapeutics, age-associated delivery barriers, clinical revolution, and emerging artificial intelligence (AI)-enabled precision therapeutic approaches to improve therapeutic outcomes in aging-associated neurodegeneration.
Dnyandev G. Gadhave, Ashish B. Jadhav, Nitin Waghamode et al.· Advanced Healthcare Material...· 1 citation
A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.
Nagaraj Rangappa, Riddhi Upadhyay, Nathish Lakshman et al.· Advances in Protein Chemistr...· 0 citations