Aug 2026· International Journal of Research in Pharmacology & Pharmacotherapeutics· 0 citations
TL;DR
This review summarizes the major causes of neurodegeneration, recent developments in advanced cell-based in vitro models, and commonly employed neuroprotective assays, highlighting their importance in the discovery of novel therapeutic agents for neurodegenerative diseases.
Abstract
Neurodegenerative diseases are progressive disorders characterized by the gradual loss of neurons, resulting in cognitive and motor impairment. The increasing prevalence of conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis has emphasized the need for effective neuroprotective therapies. In recent years, plant-derived bioactive compounds have gained significant attention because of their antioxidant, anti-inflammatory, anti-amyloidogenic, and enzyme inhibitory properties. At the same time, advances in in vitro cell-based models, including three-dimensional cultures, brain organoids, and microfluidic platforms, have improved the understanding of disease mechanisms and enhanced preclinical drug screening. In addition, various in vitro neuroprotective assays, such as acetylcholinesterase inhibition, thioflavin T amyloid aggregation, antioxidant, monoamine oxidase inhibition, lactate dehydrogenase release, and nitric oxide assays, are widely used to evaluate the neuroprotective potential of natural compounds. This review summarizes the major causes of neurodegeneration, recent developments in advanced cell-based in vitro models, and commonly employed neuroprotective assays, highlighting their importance in the discovery of novel therapeutic agents for neurodegenerative diseases.
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.
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