Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis DOI Creative Commons
Dongxiang Yuan, Shishi Jiang, Renshi Xu

et al.

Annals of Medicine, Journal Year: 2024, Volume and Issue: 56(1)

Published: Dec. 3, 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite large number studies, current prognosis ALS still not ideal. This article briefly describes clinical features including epidemiology, genetic structure and manifestations, as well progress new diagnostic criteria treatment ALS. Meanwhile, we also discussed further both developments improvements to enhance understanding accelerating introduction effective treatments

Language: Английский

Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications DOI Creative Commons
Pharaoh Fellow Mwale, Cheng-Ta Hsieh, Ting‐Lin Yen

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 18, 2025

Abstract Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player various neurodegenerative diseases brain disorders. Elevated CHI3L1 levels have been observed neurological conditions such traumatic injury (TBI), Alzheimer’s disease (AD), Parkinson’s (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob (CJD), multiple (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), tumors. This review explores the role of pathogenesis these disorders, with focus on its contributions to neuroinflammation, immune cell infiltration, neuronal degeneration. As regulator modulates microglia astrocyte activity, driving release proinflammatory cytokines that exacerbate progression. In addition pathology, promising biomarker for diagnosis monitoring cerebrospinal fluid (CSF) linked severity cognitive decline, particularly AD MS, highlighting potential clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, small-molecule inhibitors neutralizing antibodies, shown promise preclinical studies, demonstrating reduced amyloid plaque accumulation, improved survival. Despite potential, challenges remain developing selective safe CHI3L1-targeted therapies, ensuring effective delivery across blood–brain barrier mitigating off-target effects. addresses complexities highlights precision medicine, outlines future research directions aimed at unlocking full treating pathologies.

Language: Английский

Citations

2
Biomarkers for Managing Neurodegenerative Diseases DOI Open Access
Lara Cheslow, Adam E. Snook, Scott A. Waldman

et al.

Published: March 5, 2024

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% global population. Due to demographics aging, prevalence neurological disorders, including neurodegenerative diseases, will double over next two decades. Unfortunately, while available therapies provide symptomatic relief for motor impairment, there is an urgent unmet need develop disease-modifying that slow rate pathological progression. In context, biomarkers could identify at-risk prodromal patients, monitor disease progression, track response therapy, parse causality molecular events novel targets further clinical investigation. Thus, identifying discriminate between diseases reflect specific stages pathology would catalyze discovery development therapeutic targets. This review describe prevalence, known mechanisms, ongoing or recently concluded trials, three most prevalent Alzheimer’s (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s (PD).

Language: Английский

Citations

6
Biomarkers for Managing Neurodegenerative Diseases DOI Creative Commons
Lara Cheslow, Adam E. Snook, Scott A. Waldman

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 398 - 398

Published: March 26, 2024

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% global population. Due to demographics aging, prevalence neurological disorders, including neurodegenerative diseases, will double over next two decades. Unfortunately, while available therapies provide symptomatic relief for motor impairment, there is an urgent unmet need develop disease-modifying that slow rate pathological progression. In context, biomarkers could identify at-risk prodromal patients, monitor disease progression, track responses therapy, parse causality molecular events novel targets further clinical investigation. Thus, identifying discriminate between diseases reflect specific stages pathology would catalyze discovery development therapeutic targets. This review describe prevalence, known mechanisms, ongoing or recently concluded trials, three most prevalent Alzheimer’s (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s (PD).

Language: Английский

Citations

5
Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review DOI Open Access
Dong Liu,

Xin Hu,

Xiao Ding

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13437 - 13437

Published: Dec. 15, 2024

Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with chitin-binding ability but no enzymatic activity. Chi3l1 secreted by various cell types and induced several inflammatory cytokines. It can mediate series of biological processes, such proliferation, apoptosis, migration, differentiation, polarization. Accumulating evidence has verified that involved in diverse conditions; however, systematic comprehensive understanding the roles mechanisms almost all human body system-related diseases still lacking. The consists ten organ systems, which are combinations multiple organs perform one more physiological functions. Abnormalities these systems trigger environments, posing serious threats to quality life lifespan humans. Therefore, exploring novel reliable biomarkers for important, being parameter because its pathophysiological development diseases. Reportedly, plays an important role diagnosing determining disease activity/severity/prognosis related system inflammation disorders. Additionally, many studies have revealed influencing factors regulatory (e.g., ERK MAPK pathways) conditions, identifying potential therapeutic targets In this review, we comprehensively summarize underlying disorders respiratory, digestive, circulatory, nervous, urinary, endocrine, skeletal, muscular, reproductive provides Moreover, article summarizes strategies on basis mediated Chi3l1.

Language: Английский

Citations

4
Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen DOI Creative Commons
Cecilia Simonini, Elisabetta Zucchi, Ilaria Martinelli

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 1, 2025

The initiation of tofersen, a new specific antisense oligonucleotide (ASO) for SOD1 pathology, marked significant turning point SOD1-ALS patients. While clinical trials and early access program studies reported reduction in plasma cerebrospinal fluid (CSF) neurofilament levels, neuroinflammation following prolonged treatment was never assessed. In this multicenter study, we evaluated cohort 18 patients treated with analyzing correlations between biomarkers neurodegeneration/neuroinflammation variables indicative disease progression. NfL, NfH, CHI3L1, Serpina1 levels serum CSF were determined by semi-automated immunoassays (Ella™ technology). Generalized linear mixed models employed to investigate longitudinal trends these biomarkers. Our data highlighted progressive decrease during tofersen (MR = 0.97, 95% CI 0.94–0.99, p 0.006 MR 0.98, 0.95–1.00, 0.076 NfL NfH CSF, respectively). Conversely, SerpinA1 CHI3L1 increased over time 1.12, 1.08–1.16, < 0.0001 1.039, 1.015–1.062, 0.001 respectively), but modifications most apparent after six twelve months therapy, respectively. Disease progression rate did not correlate biomarker trends. We observed Tofersen treatment, alongside an increase neuroinflammatory markers, potentially linked immune response triggered ASO treatment. Given the limited on tofersen's long-term efficacy ALS due its recent introduction, identifying that predict outcomes such as diminished therapeutic or adverse effects is crucial. These may help better understand underlying pathomechanisms role modulating

Language: Английский

Citations

0
Identification and Validation of a Tear Fluid-Derived Protein Biomarker Signature in Patients with Amyotrophic Lateral Sclerosis DOI

L. Scholl,

Antonia F. Demleitner, Jan Riedel

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 16, 2025

Abstract The diagnosis of Amyotrophic Lateral Sclerosis (ALS) remains challenging, particularly in early stages, where characteristic symptoms may be subtle and nonspecific. development disease-specific clinically validated biomarkers is crucial to optimize diagnosis. Here, we explored tear fluid (TF) as a promising ALS biomarker source, given its accessibility, anatomical proximity the brainstem an important site neurodegeneration, proven discriminative power other neurodegenerative diseases. Using discovery approach, profiled protein abundance TF patients (n = 49) controls 54) via data-independent acquisition mass spectrometry. Biostatistical analysis machine learning identified differential pathways ALS, leading signature. These proteins were by Western blot independent cohort (ALS n 51; 52), their discriminatory performance was assessed in-silico employing learning. 876 consistently detected TF, with 106 differentially abundant ALS. A six-protein signature, including CRYM, PFKL, CAPZA2, ALDH16A1, SERPINC1, HP, exhibited potential. We replicated significant differences SERPINC1 HP levels between across cohorts, combination yielded best performance. Overall, this investigation proteomics revealed dysregulated pathways, highlighting inflammation key disease feature, strengthening potential source for discovery.

Language: Английский

Citations

0
The emerging role of chitinase-3-like-1 protein in neurodegeneration DOI
Veerta Sharma, Thakur Gurjeet Singh

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(5)

Published: May 21, 2025

Language: Английский

Citations

0
Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis DOI Creative Commons
Dongxiang Yuan, Shishi Jiang, Renshi Xu

et al.

Annals of Medicine, Journal Year: 2024, Volume and Issue: 56(1)

Published: Dec. 3, 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite large number studies, current prognosis ALS still not ideal. This article briefly describes clinical features including epidemiology, genetic structure and manifestations, as well progress new diagnostic criteria treatment ALS. Meanwhile, we also discussed further both developments improvements to enhance understanding accelerating introduction effective treatments

Language: Английский

Citations

2