Aug 2026· International Journal of Research in Pharmacology & Pharmacotherapeutics· Vol 15, pp. 1149-1155· 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.
In Alzheimer's disease (AD), pathological changes start decades before symptoms appear; by the time cognitive issues are noticeable, widespread neuronal and glial dysfunction and significant neuronal loss have already occurred. Recent regulatory approvals of monoclonal antibodies targeting aggregated amyloid-β (Aβ) species, including oligomers and fibrils, represent a major advance in disease-modifying therapy. However, therapeutic efficacy is strongly dependent on intervention at the earliest pathological stages, underscoring the importance of early diagnosis and treatment. Early diagnosis requires biomarkers that accurately reflect the initiation and progression of AD pathology as well as the development of methodologies capable of capturing these pathological states in vivo. Effective early treatment necessitates strategies that suppress the formation, activation, or toxicity of molecules that trigger downstream neurodegenerative cascades, thereby interrupting disease progression at its source. In parallel, advances in targeted brain delivery technologies are essential to enable sensitive detection and effective therapeutic modulation of central nervous system targets. Neurotheranostics is an integrated conceptual framework that aims to achieve early diagnosis and targeted therapy either simultaneously or in a coordinated manner using shared molecular targets and biological readouts. By unifying molecular imaging, biomarker analysis, and disease-modifying intervention, neurotheranostics aims to overcome the limitations of conventional diagnostic and therapeutic paradigms in neurodegenerative disorders, including AD. In this review, we summarize recent advances in neurotheranostic approaches for AD and highlight emerging molecular probes, low-molecular-weight compounds, and delivery technologies, including contributions from our studies.
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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
Neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, retinal neurodegeneration, and spinal cord injury represent a growing global health burden with limited therapeutic options. Natural compounds, particularly flavonoids, have emerged as promising neuroprotective agents. Naringenin (NAR), a citrus-derived flavanone, exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties. Recent studies revealed that NAR modulates multiple cellular pathways, including oxidative stress reduction, mitochondrial protection, autophagy induction, inhibition of microglial activation, and suppression of neuroinflammatory signaling such as NF-κB and NLRP3 inflammasome. Furthermore, NAR has demonstrated the ability to reduce amyloid-β plaque deposition, inhibit α-synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury. This review comprehensively summarizes the mechanistic insights and therapeutic potential of NAR across various neurodegenerative diseases, highlighting its promise as a multifunctional neuroprotective agent and the need for further translational research.
Nista Gurung, Ganesh Bohara, Nikesh Rimal et al.· Molecular Nutrition & Food R...· 0 citations
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, neuroinflammation, oxidative stress, mitochondrial dysfunction, and α-synuclein accumulation. Current treatments mainly provide symptomatic relief and do not substantially alter disease progression, highlighting the need for effective disease-modifying therapies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a potential neuroprotective agent. This narrative review evaluates the therapeutic potential of semaglutide in PD, focusing on its molecular mechanisms and preclinical and emerging clinical evidence. Experimental studies suggest that semaglutide crosses the blood-brain barrier and activates GLP-1 receptors in neuronal and glial cells, reducing microglial activation, neuroinflammation, and oxidative stress while improving mitochondrial function, cellular metabolism, and neuronal survival. It may also reduce α-synuclein aggregation and improve motor and cognitive outcomes in experimental models. Although findings are promising, clinical evidence remains limited. Well-designed randomized trials are needed to establish its efficacy, safety, optimal dosing, and disease-modifying potential in PD.
Dipesh Kumar, Renuka Sahu, Naveen Kumar et al.· International Journal of Sci...· 0 citations
Parkinson’s disease (PD) is an insidious neurodegenerative disease that is marked by loss of dopaminergic cells of the substantia nigra (SN) and aggregation of misfolded a-synuclein proteins. It is characterized by typical motor symptoms such as tremor, rigidity, bradykinesia, and postural instability, along with a wide range of non-motor manifestations including cognitive impairment, autonomic dysfunction, sleep disturbances, and mood disorders.The pathophysiology of PD is multifactorial, as it entails protein aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and genetics. Although significant advancements have been made in levodopa-based therapies and surgical interventions such as deep brain stimulation, these approaches primarily provide symptomatic relief and do not prevent disease progression. Emerging therapeutic strategies, including gene therapy, RNA-based therapeutics, immunotherapy, and stem cell interventions, are currently under investigation for their potential disease-modifying effects. Furthermore, patient-centered and precision medicine approaches are becoming increasingly important in PD management. This review integrates clinical, molecular, and therapeutic perspectives, with particular emphasis on challenges associated with bench-to-bedside translation. It also highlights the urgent need for reliable biomarkers, early diagnosis, and multidisciplinary disease-modifying strategies for future therapeutic interventions.
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