Differentiating Progressive Supranuclear Palsy and Corticobasal Syndrome: Insights from Cerebrospinal Fluid Biomarkers—A Narrative Review DOI Creative Commons
Alexandros Giannakis, Spyridon Konitsiotis, Chrissa Sioka

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(4), P. 701 - 701

Published: April 11, 2025

Background and Objectives: Despite ongoing research evolving diagnostic criteria, progressive supranuclear palsy (PSP) corticobasal syndrome (CBS) remain notoriously difficult to differentiate, largely due their overlapping clinical presentations the absence of definitive biomarkers. Materials Methods: We provide a comprehensive review cerebrospinal fluid (CSF) biomarkers, which have proven valuable in diagnosis other neurodegenerative conditions, application PSP CBS. Results: The most promising results derive from combination biomarkers associated with Parkinson’s disease, Alzheimer’s neurofilament light chain. Furthermore, CSF proteomics analysis offers insights into pathogenesis CBS could also contribute accurate diagnosis. Conclusions: hold significant potential for improving differential A stepwise approach—starting α-synuclein chain, followed by amyloid-β42 total phosphorylated tau—may clinicians practical framework distinguishing disorders. To advance this field, future efforts should prioritize large-scale, multicenter studies employing standardized methodologies enhance validity reproducibility biomarker-based diagnostics. Importantly, considering frequent pathological overlap between CBS, would greatly benefit pathology-confirmed cohorts ensure accuracy better delineate biomarker profiles across these challenging conditions.

Language: Английский

A Comprehensive Approach to Parkinson’s Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects DOI Open Access
Mauricio Muleiro Álvarez, Gabriela Cano-Herrera,

María Fernanda Osorio Martínez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7183 - 7183

Published: June 29, 2024

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by slow progression and varied symptoms. It second most common disease, over six million people in world. Its multifactorial etiology includes environmental, genomic, epigenetic factors. Clinical symptoms consist of non-motor motor symptoms, with being classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, surgical interventions. Traditional pharmacological treatment consists administering drugs (MAOIs, DA, levodopa), while emerging evidence explores potential antidiabetic agents for neuroprotection gene therapy attenuating parkinsonian Non-pharmacological treatments, such as exercise, calcium-rich diet, adequate vitamin D supplementation, aim to prevent complications. For those patients who have medically induced side effects and/or refractory surgery therapeutic option. Deep brain stimulation primary option, associated symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy portable pump succeeded reducing "off" time, where occur, increasing "on" time. This article aims address general aspects PD provide comparative comprehensive review conventional latest advancements treatments PD. Nevertheless, further studies are required optimize suitable alternatives.

Language: Английский

Citations

16
The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications DOI Open Access
Sehwan Kim, Un Ju Jung, Sang Ryong Kim

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

Citations

5
Associations Between Diabetes Mellitus and Neurodegenerative Diseases DOI Open Access

Leszek Szablewski

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 542 - 542

Published: Jan. 10, 2025

Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years older type 2 diabetes (T2DM) cognitive impairment. It was found that is a major risk for decline, dementia, Parkinson's disease (PD), Alzheimer's (AD), Huntington's (HD), amyotrophic lateral sclerosis (ALS) other disorders. Different mechanisms of associations between these diseases have been suggested. For example, it postulated an impaired intracellular insulin signaling pathway, together with hyperglycemia hyperinsulinemia, may cause pathological changes, such as dysfunction the mitochondria, oxidative stress inflammatory responses, etc. association diseases, well associations, needs further investigation. aim this review to describe mellitus, especially 1 (T1DM) selected i.e., disease, sclerosis. Suggested also described.

Language: Английский

Citations

3
Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions DOI Creative Commons
Grace m. Kuo, Ramhari Kumbhar,

W. Frank Blair

et al.

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

Published: Jan. 23, 2025

Abstract α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson’s disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer’s concurrent with LBD (AD-LBD). These disorders are unified by pathological hallmark: aberrant misfolding accumulation α-synuclein (α-syn). This review delves into the pivotal role α-syn, key agent in α-synucleinopathy pathophysiology, provides survey potential therapeutics that target cell-to-cell spread pathologic α-syn. Recognizing intricate complexity multifactorial etiology α-synucleinopathy, illuminates various membrane receptors, proteins, intercellular spreading pathways, agents for therapeutic interventions. While significant progress has been made understanding pursuit efficacious treatments remains challenging. Several strategies involving decreasing α-syn production aggregation, increasing degradation, lowering extracellular inhibiting cellular uptake presented. The paper underscores necessity meticulous comprehensive investigations to advance our knowledge pathology ultimately develop innovative α-synucleinopathies. Graphical

Language: Английский

Citations

3
Mechanistic insights on TLR-4 mediated inflammatory pathway in neurodegenerative diseases DOI
Veerta Sharma,

Prateek Sharma,

Thakur Gurjeet Singh

et al.

Pharmacological Reports, Journal Year: 2024, Volume and Issue: 76(4), P. 679 - 692

Published: June 25, 2024

Language: Английский

Citations

14
Multi-functional role of apolipoprotein E in neurodegenerative diseases DOI Creative Commons
Sadequl Islam, Arshad Ali Noorani, Yang Sun

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 29, 2025

Genetic diversity in the apolipoprotein E (ApoE) gene has been identified as major susceptibility genetic risk factor for sporadic Alzheimer’s disease (SAD). Specifically, ApoEε4 allele is a significant SAD, while ApoEε2 provides protection compared to more common ApoEε3 allele. This review discusses role of ApoE AD and other neurodegenerative disorders. ApoE, cholesterol transport protein, influences several pathways involved neurodegeneration, particularly AD. Beyond its established amyloid β -protein (Aβ) metabolism deposition, also impacts tau pathology, microglial response The aims provide an updated overview ApoE’s diverse roles, emphasizing involvement Aβ clearance through receptors. It covers influence diseases like Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Huntington’s (HD), vascular dementia (VD), multiple (MS). New research highlights interaction between presenilin (PS), suggesting connections familial (FAD) SAD. explores protective effects mutations against ApoE4-induced tauopathy, neuroinflammation. insights from this comprehensive update could indeed lead new therapeutic strategies diseases.

Language: Английский

Citations

1
A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease DOI Creative Commons
Dunhui Li, Wai Yan Yau,

Shengdi Chen

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 4, 2025

Based on the prevailing α-synuclein "gain-of-function" hypothesis, reducing levels and removing its aggregates is a current focus of disease-modifying therapies for Parkinson's disease. Emerging evidence "loss-of-function" suggests that it may be necessary to replenish monomeric levels. We propose personalized comprehensive approach different subgroups based whether likely contribute disease pathogenesis through "gain-of-function", "loss-of-function", or both mechanisms.

Language: Английский

Citations

1
Are Therapies That Target α-Synuclein Effective at Halting Parkinson’s Disease Progression? A Systematic Review DOI Open Access

A. Rodger,

Maryam N. ALNasser, Wayne G. Carter

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11022 - 11022

Published: July 3, 2023

There are currently no pharmacological treatments available that completely halt or reverse the progression of Parkinson’s Disease (PD). Hence, there is an unmet need for neuroprotective therapies. Lewy bodies a neuropathological hallmark PD and contain aggregated α-synuclein (α-syn) which thought to be neurotoxic therefore suitable target therapeutic interventions. To investigate this further, systematic review was undertaken evaluate whether anti-α-syn therapies effective at preventing in preclinical vivo models via current human clinical trials. An electronic literature search performed using MEDLINE EMBASE (Ovid), PubMed, Web Science Core Collection, Cochrane databases collate evidence investigated targeting α-syn. Novel therapeutics provided significant reduction α-syn aggregations. Biochemical immunohistochemical analysis rodent brain tissue demonstrated reduced α-syn-associated pathology rescued dopaminergic neuronal loss. Some studies did not provide endpoints since they had yet been completed were terminated before completion. Completed trials displayed tolerability efficacy reducing patients with minimal adverse effects. Collectively, highlights capacity reduce accumulation both potential optimism further restrict loss and/or prophylactic protection avoid onset α-syn-induced PD.

Language: Английский

Citations

20
The Complex Interplay between Toxic Hallmark Proteins, Calmodulin-Binding Proteins, Ion Channels, and Receptors Involved in Calcium Dyshomeostasis in Neurodegeneration DOI Creative Commons
Danton H. O’Day

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 173 - 173

Published: Jan. 31, 2024

Calcium dyshomeostasis is an early critical event in neurodegeneration as exemplified by Alzheimer’s (AD), Huntington’s (HD) and Parkinson’s (PD) diseases. Neuronal calcium homeostasis maintained a diversity of ion channels, buffers, calcium-binding protein effectors, intracellular storage the endoplasmic reticulum, mitochondria, lysosomes. The function these components compartments impacted toxic hallmark proteins AD (amyloid beta Tau), HD (huntingtin) PD (alpha-synuclein) well interactions with downstream proteins, especially calmodulin. Each beta, Tau, huntingtin, alpha-synuclein) binds to Multiple channels receptors involved dysregulation also bind are regulated primary goal this review show complexity how they can impact research search for therapies. A secondary suggest that therapeutic targets from may offer greater opportunities success.

Language: Английский

Citations

6
The Contribution of Type 2 Diabetes to Parkinson’s Disease Aetiology DOI Open Access
Samo Ribarič

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4358 - 4358

Published: April 15, 2024

Type 2 diabetes (T2D) and Parkinson’s disease (PD) are chronic disorders that have a significant health impact on global scale. Epidemiological, preclinical, clinical research underpins the assumption insulin resistance inflammation contribute to overlapping aetiologies of T2D PD. This narrative review summarises recent evidence contribution initiation progression PD brain pathology. It also briefly discusses rationale potential alternative pharmacological interventions for treatment.

Language: Английский

Citations

5