Aug 2026· Advanced Healthcare Materials· pp.
e71594
· 1 citation· 245 references
Medicine
TL;DR
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.
Abstract
Aging is a significant risk factor of neurodegenerative disorders (NDs) such as Huntington's, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Although several clinical, neuroimaging, and biomarker-based diagnostic approaches are available for NDs, their limited sensitivity for early-stage detection, disease specificity, and prediction of disease progression continue to present significant clinical challenges, often resulting in delayed diagnosis and therapeutic intervention. According to previously published works, the preliminary pathological feature of such disorders is mitochondrial dysfunction. This may lead to elevated oxidative stress, impaired mitophagy, unbalanced mitochondrial function, and bioenergetic failure. This review examines how mitochondria-targeted nanotherapeutic approaches can overcome these pathological barriers and improve therapeutic outcomes in aging-associated neurodegeneration. Targeted delivery of drug-loaded nanocarriers, such as gene-delivery, lipid-based, metallic, and polymeric nanoparticles, has emerged as a potential platform to deliver medication directly to defective mitochondria. It may increase mitochondrial biogenesis, maintain redox balance, and protect against neuronal degeneration. 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. Mitochondria-targeted nanotherapeutics depict a potential disease-modifying strategy for aging-related NDs. However, further advancements in targeting efficacy, scalable production, long-term safety, and clinical validation can facilitate a successful clinical revolution.
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
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
Parkinson's disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. Its clinical features include motor symptoms such as tremor, bradykinesia, rigidity, and postural instability. The pathophysiology of PD involves oxidative stress, mitochondrial impairment, neuroinflammation, protein misfolding, and aberrant alpha-synuclein aggregation, which disrupt dopaminergic signaling pathways. Biomarkers such as α-synuclein, DJ-1, neurofilament light chain, and imaging biomarkers such as DAT-SPECT are being studied for early diagnosis, evaluation of disease progression, and therapy monitoring. Although advancements have been made, current options-such as dopamine replacement therapy, deep brain stimulation, and physiotherapy-remain largely symptomatic, carry long-term side effects, and fail to halt disease progression. Nanotechnology advancements have brought a major paradigm shift in the management of PD. Curcumin, Resveratrol, and EGCG are bioactive compounds with antioxidant, anti-inflammatory, and neuroprotective properties. However, their clinical use is limited because of poor bioavailability and stability. Nanocarrier systems such as liposomes, dendrimers, and polymeric nanoparticles improve targeted delivery through the blood-brain barrier. This helps in reducing systemic toxicity and enhancing therapeutic effectiveness. The therapeutic mechanism of these nanoformulations mainly involves free radical scavenging, modulation of mitochondrial function, inhibition of α-synuclein fibril formation, and regulation of cell signal transduction pathways such as Nrf2/ARE and NF-κB. The major challenges include large-scale production, long-term safety assessment, regulatory challenges, and site-specific delivery. Future research is moving toward the convergence of gene therapy, nanomedicine, and precision targeting to develop disease-modifying therapy. This approach aims not only to control symptoms but also to potentially control neurodegeneration in PD.
P. Gaur, Prachee Raje Bisht, Sonia Lal Gupta· Journal of Biomaterials Scie...· 0 citations
Alzheimer's Disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive and behavioral impairment and represents a major cause of dementia worldwide. It primarily affects the elderly population. The disease is marked by progressive neuronal damage, leading to impairments in cognition, behavior, emotions, and communication. Although currently available therapies provide symptomatic relief, they fail to alter disease progression, necessitating the development of more effective therapeutic strategies. Phytoconstituents have gained considerable attention due to their neuroprotective properties and multitargeted mechanisms of action against pathways implicated in AD. However, their clinical application is limited by poor Blood-Brain Barrier (BBB) permeability, low bioavailability, and inadequate solubility. Nanotechnology offers a promising approach for brain-targeted drug delivery by enhancing the therapeutic efficacy of phytoconstituents through advanced nanocarrier systems. This review explores the synergistic potential of phytoconstituents and nanocarriers for the management of AD, aiming to improve therapeutic outcomes and overcome existing limitations. It further highlights the integration of medicinal plant-based compounds with nanotechnology as a novel strategy for AD treatment. The combination of nanocarriers and phytoconstituents may facilitate enhanced BBB penetration and improved neuroprotection. Notably, nanomedicine- based approaches, including phytoconstituent-loaded nanoparticles and liposomes, demonstrate significant potential to overcome delivery barriers and enable efficient drug transport to the brain.
Anushka Sharma, Awaneet Kaur, Javed Khan et al.· Central Nervous System Agent...· 0 citations