Peripheral proteinopathy in neurodegenerative diseases

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 16, 2025

Proteinopathies in neurology typically refer to pathological changes proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau Alzheimer's disease, α-synuclein Parkinson's disease multiple system atrophy, TAR DNA-binding protein 43 amyotrophic lateral sclerosis frontotemporal dementia. Interestingly, these are also commonly found peripheral tissues, raising important questions about their roles disorders. Multiple studies have shown that peripherally derived not only travel brain through various routes, aggravating pathology, but contribute significantly dysfunction, highlighting crucial impact on diseases. Investigating how influence progression disorders could open new horizons for achieving early diagnosis treatment. This review summarizes distribution, transportation pathways, pathogenic mechanisms several neurodegenerative disease-related periphery, proposing targeting be a promising strategy preventing managing

Language: Английский

Repurposing Antimicrobial Protegrin-1 as a Dual-Function Amyloid Inhibitor via Cross-seeding

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(17), P. 3143 - 3155

Published: Aug. 17, 2023

Amyloids and antimicrobial peptides have traditionally been recognized as distinct families with separate biological functions targets. However, certain amyloids share structural functional characteristics that contribute to the development of neurodegenerative diseases. Specifically, aggregation amyloid-β (Aβ) microbial infections are interconnected pathological factors in Alzheimer's disease (AD). In this study, we propose demonstrate a novel repurposing strategy for an peptide protegrin-1 (PG-1), which exhibits ability simultaneously prevent Aβ infection both vitro vivo. Through comprehensive analysis using protein, cell, worm assays, uncover multiple PG-1 against Aβ, including following: (i) complete inhibition at low molar ratio PG-1/Aβ = 0.25:1, (ii) disassembly preformed fibrils into amorphous aggregates, (iii) reduction Aβ-induced cytotoxicity SH-SY5Y cells transgenic GMC101 nematodes, (iv) preservation original activity P.A., E.coli., S.A., S.E. strains presence Aβ. Mechanistically, dual anti-amyloid anti-bacterial primarily arise from its strong binding seeds (KD 1.24-1.90 μM) through conformationally similar β-sheet associations. This work introduces promising repurpose amyloid inhibitors, effectively targeting pathways AD.

Language: Английский

Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition

Endocrine Practice, Journal Year: 2024, Volume and Issue: 30(4), P. 311 - 318

Published: Jan. 5, 2024

ObjectiveAmyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact amyloid status on survival outcomes in large cohort.MethodsThe Surveillance, Epidemiology, and End Results registry was queried identify patients diagnosed with MTC from 2000-2019. Patients positive (ICD-O-3 code 8345/3) negative 8510/3) tumors were analyzed. Overall disease-specific compared between matched cohorts using Kaplan-Meier Cox proportional hazards analyses.ResultsOf 2,526 patients, 511 which 2,015 that negative. Amyloid displayed lower T stage (T3/4: 28% vs 85%, p<0.001) less extrathyroidal extension (11.3% 81.6%, p<0.001). No difference distant metastasis rate observed groups (14.5% 14.4%, p=0.98). showed tendency for distal lymph node (1.2% 0.3%, p=0.020). On univariate analysis, comparable overall times (mean 172.2 177.8 months, p=0.17), but trend toward worse cancer-specific (HR=1.31, 95%CI=0.99-1.71, p=0.051). After adjusting covariates, did not independently predict (HR=1.15, 95%CI=0.91-1.47, p=0.25) or (HR=1.30, 95%CI=0.96-1.77, p=0.09). Initiating therapy later than one month following diagnosis associated (HR=1.25, 95%CI=1.02-1.54, p=0.029).ConclusionsThe presence paradoxically associates yet exhibits towards mortality. alone does influence prognosis. Delayed treatment adversely impacted survival.

Language: Английский