Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 259 - 259

Published: April 8, 2025

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) are characterized progressive neuronal loss cognitive or motor decline, often underpinned pathological protein misfolding aggregation. Emerging evidence suggests potential mechanistic link between chronic NDs, with contributing neuroinflammatory states homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis aggregation serve bridge We systematically examine molecular pathways misfolding, proteostasis dysfunction shared neuroimmune mechanisms, highlighting prion-like propagation misfolded proteins, neuroinflammation, oxidative stress common denominators. further discuss from experimental models clinical studies linking accelerated pathology—including tau accumulation, amyloid dysregulation, microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting aggregation, enhancing chaperone function, modulating unfolded response (UPR), attenuating glial activation explored strategies mitigate possibly slow Understanding this intersection not only elucidates pain’s role decline but also interventions addressing inflammation could yield dual benefits management modification.

Language: Английский

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Hydrophobic Carbon Dots Prevent α‐Synucleinopathy and Suppress Neuroinflammation to Treat Parkinson's Disease

Aggregate, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

ABSTRACT The aggregation of α‐synuclein (ɑ‐syn) coupled with overexpressed neuroinflammation instigates the degeneration dopaminergic neurons, thereby aggravating progression Parkinson's disease (PD). Herein, we introduced a series hydrophobic amino acid–based carbon dots (CDs) for inhibiting ɑ‐syn and mitigating inflammation in PD neurons. Significantly, show phenylalanine CDs (Phe‐CDs) could strongly bind monomers dimers via force, maintain their stability, inhibit further aggregates situ vitro, finally conferring neuroprotection by rescuing synaptic loss, ameliorating mitochondrial dysfunctions, modulating Ca 2+ flux. Importantly, Phe‐CDs demonstrate ability to penetrate blood–brain barrier (BBB), significantly improving motor performance mice. Our findings suggest that hold great promise as therapeutic agent relative neurodegenerative disease.

Language: Английский

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DNA-Assisted CRISPR-Cas12a Enhanced Fluorescent Assay for Protein Detection in Complicated Matrices

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Proteins are important biological macromolecules that perform a wide variety of functions in the cell and human body, can serve as biomarkers for early diagnosis prognosis diseases well monitoring effectiveness disease treatment. Hence, sensitive accurate detection proteins biospecimens is imperative. However, at present, there no ideal method available clinical samples, many which present ultralow (less than 1 pM) concentrations complicated matrices. Herein, we report an ultrasensitive selective DNA-assisted CRISPR-Cas12a enhanced fluorescent assay (DACEA) protein with limits reaching low attomolar concentrations. The high sensitivity was accomplished through combined DNA barcode amplification (by using dual-functionalized AuNPs) CRISPR analysis, while selectivity resistance to matrix effects our were via formation protein-antibody sandwich structure specific recognition Cas12a (under guidance crRNA) toward designed target ssDNA. Given its ability accurately sensitively detect trace amounts matrices, DACEA platform pioneered this work has potential application routine biomarker testing.

Language: Английский

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Brain derived β-interferon is a potential player in Alzheimer’s disease pathogenesis and cognitive impairment

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 21, 2024

Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in pathogenesis Alzheimer's disease (AD). However, precise types interferons and related cytokines, both from brain periphery, responsible for cognitive impairment patients with AD remain unclear. A total 131 participants (78 [59.5%] female 53 [40.5%] male; mean [SD] age, 61.5 [7.6] years) normal cognition China Aging Neurodegenerative Initiative cohort were included. CSF serum IFNα-2a, IFN-β, IFN-γ, TNF-α, IL-6, IL-10, MCP-1and CXCL-10 tested. The correlation between these cytokines core biomarkers plasma, performance, MRI measures analysed. We found only IFN-β levels significantly elevated compared to cognition. Furthermore, associated (CSF P-tau Aβ42/Aβ40 ratio) performance (MMSE CDR score). Additionally, correlated typical pattern atrophy (such as hippocampus, amygdala, precuneus). In contrast, IL-6 non-AD cognitively impaired other groups. Moreover, individuals vascular impairment-related markers white matter hyperintensity). Our findings demonstrate distinct inflammatory molecules are different disorders. Notably, linked pathology AD, identifying this interferon a potential target therapy.

Language: Английский

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Chronological versus immunological aging: Immune rejuvenation to arrest cognitive decline

Neuron, Journal Year: 2024, Volume and Issue: 113(1), P. 140 - 153

Published: Dec. 27, 2024

Language: Английский

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