Amyloid fibrils act as a reservoir of soluble oligomers, the main culprits in protein deposition diseases

BioEssays, Journal Year: 2022, Volume and Issue: 44(11)

Published: Sept. 14, 2022

Amyloid fibril formation plays a central role in the pathogenesis of number neurodegenerative diseases, including Alzheimer and Parkinson diseases. Transient prefibrillar oligomers forming during aggregation process, exhibiting small size large hydrophobic surface, can aberrantly interact with molecular targets on neurons, lipid bilayer plasma membranes, resulting fatal outcome for cells. By contrast, mature fibrils, despite presenting generally high are endowed low diffusion rate poorly penetrate interior bilayer. However, increasing evidence shows that both intracellular α-synuclein as well extracellular amyloid-β β2-microglobulin release over time quickly diffuse to reach membrane neighboring The persistent leakage harmful from fibrils triggers an ongoing cascade events sustained injury neurons glia also provides aggregates ability cross biological membranes between cells or cellular compartments.

Language: Английский

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The Sigma Receptors in Alzheimer’s Disease: New Potential Targets for Diagnosis and Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12025 - 12025

Published: July 27, 2023

Sigma (σ) receptors are a class of unique proteins with two subtypes: the sigma-1 (σ1) receptor which is situated at mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), and sigma-2 (σ2) receptor, located in ER-resident membrane. Increasing evidence indicates involvement both σ1 σ2 pathogenesis Alzheimer’s disease (AD), thus these represent potentially effective biomarkers for emerging AD therapies. The availability optimal radioligands positron emission tomography (PET) neuroimaging humans will provide tools to monitor progression treatment outcomes. In this review, we first summarize significance pathophysiology highlight therapeutic strategies related receptors. We then survey potential PET radioligands, an emphasis on requirements imaging or humans. Finally, discuss current challenges development receptors, opportunities elucidate as novel early diagnosis, monitoring drug efficacy.

Language: Английский

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Dauricine alleviates cognitive impairment in Alzheimer's disease mice induced by D-galactose and AlCl3 via the Ca2+/CaM pathway

Toxicology and Applied Pharmacology, Journal Year: 2023, Volume and Issue: 474, P. 116613 - 116613

Published: July 5, 2023

Language: Английский

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Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102633 - 102633

Published: Feb. 17, 2023

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) its metabolites (acid-labile (e.g., iron-sulfur clusters) bound per-, poly-) sulfides) have been shown modulate both neuronal homeostasis. We recently reported elevated plasma sulfides were associated with cognitive dysfunction measures microvascular in ADRD. Here we extend our previous work show associations between magnetic resonance-based metrics brain atrophy white matter integrity. Elevated decreased grey volume, while increased acid labile integrity greater ventricular volume. These findings are consistent alterations metabolism ADRD which may represent maladaptive responses oxidative stress.

Language: Английский

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Emerging therapeutics agents and recent advances in drug repurposing for Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 85, P. 101815 - 101815

Published: Dec. 16, 2022

Language: Английский

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