Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer’s and Parkinson’s Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 9082 - 9082

Published: Aug. 23, 2021

Neurodegenerative disorders involve the slow and gradual degeneration of axons neurons in central nervous system (CNS), resulting abnormalities cellular function eventual demise. Patients with these succumb to high medical costs disruption their normal lives. Current therapeutics employed for treating diseases are deemed palliative. Hence, a treatment strategy that targets disease’s cause, not just symptoms exhibited, is desired. The synergistic use nanomedicine gene therapy effectively target causative mutated gene/s CNS disease progression could provide much-needed impetus this battle against diseases. This review focuses on Parkinson’s Alzheimer’s diseases, proteins responsible damage death neurons, importance as potential strategy. Multiple genes were identified regard, each presenting various mutations. genome-wide sequencing essential specific patients. While cure yet be achieved, genomic studies form basis creating highly efficacious nanotherapeutic can eradicate dreaded Thus, lead way helping millions people worldwide eventually better life.

Language: Английский

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Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(10), P. 3743 - 3782

Published: June 11, 2022

UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and homologous protein of autophagy related (Atg) yeast UNC-51 Caenorhabditis elegans. ULK1 well-known for activation, which evolutionarily conserved transport indispensable to maintain cell homeostasis. As the direct target energy nutrition-sensing may contribute distribution utilization cellular resources response metabolism closely associated with multiple pathophysiological processes. Moreover, has been widely reported play crucial role human diseases, including cancer, neurodegenerative cardiovascular disease, infections, subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, non-autophagy function emerging, indicating that non-autophagy-relevant signaling network linked diseases under some specific contexts. Therefore, this review, we summarized structure functions initiator, focus on new approaches, further elucidated key roles non-autophagy. Additionally, discussed relationships between well illustrated rapid progress better understanding discovery more candidate drugs targeting ULK1, will provide clue novel ULK1-targeted therapeutics future.

Language: Английский

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Rational design and combinatorial chemistry of ionizable lipids for RNA delivery

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(28), P. 6527 - 6539

Published: Jan. 1, 2023

This review will delve into the crucial role of ionizable lipids in development lipid nanoparticles (LNPs) for efficient RNA delivery.

Language: Английский

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Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 13, 2023

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells eventually death. Drug delivery for treatment effected nervous system is notoriously complicated because presence natural barriers, i.e., blood-brain barrier blood cerebrospinal fluid barrier. Palliative care currently standard many diseases. Therefore, programs that target disease's origin rather than its symptoms are recommended. Nanotechnology-based drug platforms offer an innovative way circumvent these obstacles deliver medications directly central system, thereby enabling several common neurological problems, Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis. Interestingly, combination nanomedicine gene therapy enables targeting selective mutant genes responsible progression NDs, which may provide a much-needed boost struggle against Herein, we discussed various obstacles, followed by detailed insight into recently developed techniques restore function via differentiation neural stem cells. Moreover, comprehensive background on role controlling neurogenesis explained. Additionally, numerous phytoconstituents with neuroprotective properties molecular targets identification management NDs also deliberated. Furthermore, ongoing clinical trials marketed products provided this manuscript.

Language: Английский

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Exploring the Causal Relationship Between Telomere Biology and Alzheimer’s Disease

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(8), P. 4169 - 4183

Published: April 12, 2023

Telomeres, also known as the "protective caps" of our chromosomes, shorten with each cell cycle due to end replication problem. This process, termed telomere attrition, is associated many age-related disorders, such Alzheimer's disease (AD). Despite numerous studies conducted in this field, role attrition onset remains unclear. To investigate causal relationship between short telomeres and AD, review aims highlight primary factors that regulate length maintain its integrity, an additional outlook on oxidative stress, which commonly aging molecular damage. Although some findings thus far might be contradictory, likely plays a crucial progression AD close association stress. The currently available treatments for are only symptomatic without affecting disease. components biology discussed paper have previously been studied alternative treatment option several diseases exhibited promising vitro vivo results. Hence, should provide basis future research develop potential therapeutic strategy AD. (Created BioRender.com).

Language: Английский

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From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer’s Disease

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

Language: Английский

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Computational Frontiers in Aptamer-Based Nanomedicine for Precision Therapeutics: A Comprehensive Review

ACS Omega, Journal Year: 2024, Volume and Issue: 9(25), P. 26838 - 26862

Published: June 10, 2024

In the rapidly evolving landscape of nanomedicine, aptamers have emerged as powerful molecular tools, demonstrating immense potential in targeted therapeutics, diagnostics, and drug delivery systems. This paper explores computational features highlighting their advantages over antibodies, including selectivity, low immunogenicity, a simple production process. A comprehensive overview aptamer development process, specifically Systematic Evolution Ligands by Exponential Enrichment (SELEX) sheds light on intricate methodologies behind selection. The historical evolution diverse applications nanomedicine are discussed, emphasizing pivotal role delivery, precision medicine therapeutics. Furthermore, we explore integration artificial intelligence (AI), machine learning (ML), Internet Things (IoT), Medical (IoMT), nanotechnology aptameric development, illustrating how these cutting-edge technologies revolutionizing selection optimization for tailored biomedical applications. also discusses challenges methods advancing aptamers, reliable prediction models, extensive data analysis, multiomics incorporation. It addresses ethical concerns restrictions related to AI IoT use research. examines progress computer simulations nanomedicine. By elucidating importance understanding superiority exploring context challenges, this review serves valuable resource researchers practitioners aiming harness full field

Language: Английский

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Microglia-targeting nanotherapeutics for neurodegenerative diseases

APL Bioengineering, Journal Year: 2020, Volume and Issue: 4(3)

Published: Sept. 1, 2020

Advances in nanotechnology have enabled the design of nanotherapeutic platforms that could address challenges targeted delivery active therapeutic agents to central nervous system (CNS). While majority previous research studies on CNS nanotherapeutics focused neurons and endothelial cells, predominant resident immune cells CNS, microglia, are also emerging as a promising cellular target for neurodegeneration considering their prominent role neuroinflammation. Under normal physiological conditions, microglia protect by removing pathological agents. However, long-term exposure stimulants will cause sustained activation lead neuronal damage due release pro-inflammatory agents, resulting neuroinflammation neurodegeneration. This Perspective highlights criteria be considered when designing microglia-targeting treatment neurodegenerative disorders. These include conjugating specific microglial receptor-targeting ligands or peptides nanoparticle surface achieve delivery, leveraging phagocytic properties, utilizing biocompatible biodegradable nanomaterials with low reactivity neurotoxicity. In addition, certain controlled inhibition toxic protein aggregation modulation pathways can incorporated within structure without compromising stability. Overall, multifaceted disease mechanisms neurodegeneration, microglia-targeted nanodrugs particles may potential resolve multiple determinants guide shift phenotype spectrum toward more neuroprotective state.

Language: Английский

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Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 59(1), P. 191 - 233

Published: Oct. 15, 2021

Language: Английский

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Future Prospects of Gene Therapy for Friedreich’s Ataxia

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1815 - 1815

Published: Feb. 11, 2021

Friedreich’s ataxia is an autosomal recessive neurogenetic disease that mainly associated with atrophy of the spinal cord and progressive neurodegeneration in cerebellum. The caused by a GAA-expansion first intron frataxin gene leading to decreased level protein, which results mitochondrial dysfunction. Currently, there no effective treatment delay ataxia. A plausible therapeutic approach therapy. Indeed, mouse models have been treated viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, therapy increasingly consolidating one most therapies. However, several hurdles be overcome, including immunotoxicity pheno-toxicity. We review state art ataxia, addressing main challenges feasible solutions them.

Language: Английский

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