Therapeutic Strategies in Huntington’s Disease: From Genetic Defect to Gene Therapy DOI Creative Commons
Anamaria Jurcău, Maria Carolina Jurcău

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 1895 - 1895

Published: Aug. 5, 2022

Despite the identification of an expanded CAG repeat on exon 1 huntingtin gene located chromosome as genetic defect causing Huntington’s disease almost 30 years ago, currently approved therapies provide only limited symptomatic relief and do not influence age onset or progression rate. Research has identified various intricate pathogenic cascades which lead to neuronal degeneration, but interfering with these mechanisms have been marked by many failures remain be validated. Exciting new opportunities are opened emerging techniques target mutant protein DNA RNA, allowing for “gene editing”. Although some issues relating “off-target” effects immune-mediated side need solved, strategies, combined stem cell more traditional approaches targeting specific cascades, such excitotoxicity bioavailability neurotrophic factors, could significant improvement outcomes treated patients.

Language: Английский

The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets DOI Creative Commons

Alhamdu Adamu,

Shuo Li,

Fankai Gao

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 12, 2024

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.

Language: Английский

Citations

89
Current and Possible Future Therapeutic Options for Huntington’s Disease DOI Creative Commons

Mackenzie Wendy Ferguson,

Connor J. Kennedy,

Thulani H. Palpagama

et al.

Journal of Central Nervous System Disease, Journal Year: 2022, Volume and Issue: 14

Published: April 1, 2022

Huntington's disease (HD) is an autosomal neurodegenerative that characterized by excessive number of CAG trinucleotide repeats within the huntingtin gene (

Language: Английский

Citations

80
Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review DOI Creative Commons
Lucas Fornari Laurindo,

Gabriel Magno de Carvalho,

Bárbara de Oliveira Zanuso

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(1), P. 229 - 229

Published: Jan. 10, 2023

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR’s numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve solubility bioavailability potentialize its health effects. This review investigated different CUR-based nanomedicines inflammatory immunomodulated diseases. PUBMED, EMBASE, COCHRANE, GOOGLE SCHOLAR databases were searched, Scale for Assessment Narrative Review Articles (SANRA) was used quality assessment PRISMA guidelines. Overall, 66 studies included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS), Huntington’s (HD), bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, COVID-19. The available scientific show there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, liposomes. These formulations CUR effectively adjuvants several immune-mediated atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, COVID-19, anti-fibrotic fibrotic disease.

Language: Английский

Citations

52
Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases DOI Open Access

Jing Pan,

Chen-Jie Fei,

Yang Hu

et al.

动物学研究, Journal Year: 2023, Volume and Issue: 44(1), P. 183 - 218

Published: Jan. 1, 2023

The innate immune system protects the host from external pathogens and internal damage in various ways. cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS), stimulator interferon genes (STING), downstream adaptors, plays an essential role protective defense against microbial DNA damaged-associated is responsible for immune-related diseases. After binding with DNA, cytosolic cGAS undergoes conformational change DNA-linked liquid-liquid phase separation to produce 2'3'-cGAMP activation endoplasmic reticulum (ER)-localized STING. However, further studies revealed that predominantly expressed nucleus strictly tethered chromatin prevent nuclear functions differently cytosolic-localized cGAS. Detailed delineation this including its structure, signaling, regulatory mechanisms, great significance fully understand diversity will be benefit treatment inflammatory diseases cancer. Here, we review recent progress on above-mentioned perspectives pathway discuss new avenues study.

Language: Английский

Citations

51
Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications DOI Open Access
Paras Mani Giri, Anurag Banerjee,

Arpita Ghosal

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3995 - 3995

Published: April 3, 2024

Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of total population world is affected by some form NDs, resulting in physical and cognitive disability. The most NDs include Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease. Although are caused a complex interaction genetic, environmental, lifestyle variables, neuroinflammation known to be associated with all often leading permanent damage neurons central nervous system. Furthermore, numerous emerging pieces evidence demonstrated that inflammation not only supports progression but can also serve as an initiator. Hence, various medicines capable preventing or reducing been investigated ND treatments. While anti-inflammatory medicine has shown promising benefits several preclinical models, clinical outcomes questionable. In this review, we discuss their current treatment strategies, role pathophysiology use agents potential therapeutic option.

Language: Английский

Citations

30
Unveiling the interplay of AMPK/SIRT1/PGC-1α axis in brain health: Promising targets against aging and NDDs DOI
Pratik Shankar Rakshe, Bhaskar Jyoti Dutta, Shivani Chib

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102255 - 102255

Published: March 14, 2024

Language: Английский

Citations

23
The impact of air pollution on neurodegenerative diseases: a narrative review of current evidence DOI Creative Commons
Nicholas Aderinto,

Ayobami Ajagbe,

Gbolahan Olatunji

et al.

The Egyptian Journal of Internal Medicine, Journal Year: 2025, Volume and Issue: 37(1)

Published: Jan. 24, 2025

Abstract This narrative review explores the relationship between air pollution and neurodegenerative diseases (NDs). Historically, has been linked primarily to respiratory cardiovascular issues, but recent evidence suggests that it may also impact neurological health. With global increase in diseases, understanding environmental risk factors become crucial. The synthesizes findings from studies, highlighting potential role of pollutants—particularly fine particulate matter (PM2.5), ozone, nitrogen dioxide (NO2), heavy metals—in onset progression NDs. Key mechanisms under investigation include brain inflammation microglial activation, which are believed contribute processes. Animal human studies have shown correlations exposure increased cognitive decline disorders. Research indicates exacerbate neuroinflammation cause white abnormalities, disrupt neural communication function. Additionally, emerging like residential greenness climate action could mitigate some these adverse effects. Despite advancements, significant knowledge gaps remain, particularly regarding long-term chronic specific molecular pathways involved. shows need for further research clarify develop targeted interventions. Addressing pollution’s on requires comprehensive public health strategies, including stricter regulations awareness, alongside continued into preventive therapeutic measures.

Language: Английский

Citations

3
Neuroinflammation and neurodegeneration in Huntington’s disease: genetic hallmarks, role of metals and organophosphates DOI

Omkar Kumar Kunwar,

Shamsher Singh

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 17, 2025

Language: Английский

Citations

2
Genistein: A Promising Ally in Combating Neurodegenerative Disorders DOI

Diksha Sharma,

Varinder Singh, Amit Kumar

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177273 - 177273

Published: Jan. 1, 2025

Language: Английский

Citations

2
The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders DOI Creative Commons

Tadahiro Numakawa,

Ryutaro Kajihara

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 848 - 848

Published: Feb. 12, 2025

Among neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4/5), BDNF has been extensively studied for its physiological role in cell survival synaptic regulation the central nervous system's (CNS's) neurons. binds to TrkB (a tyrosine kinase) with high affinity, resulting downstream intracellular signaling cascades play crucial roles determining fate, neuronal differentiation maturation of CNS It well demonstrated that downregulation/dysregulation BDNF/TrkB system is implicated pathogenesis neurologic psychiatric disorders, such as Alzheimer's disease (AD) depression. Interestingly, effects mimetic compounds flavonoids, small molecules which can activate TrkB-mediated signaling, have investigated potential therapeutic strategies brain diseases, given p75NTR, a common neurotrophin receptor, also contributes death under variety pathological conditions neurodegeneration. Since downregulation associated pathophysiology neurodegenerative diseases understanding how alterations contribute progression could provide valuable insight prevention these diseases. The present review shows recent advances molecular mechanisms underlying plasticity, providing critical insights into impact mimetics

Language: Английский

Citations

2