An 11-mer Synthetic Peptide Suppressing Aggregation of Aβ25-35 and Resolving Its Aggregated Form Improves Test Performance in an Aβ25-35-Induced Alzheimer’s Mouse Model DOI Creative Commons
Rina Nakamura, Akira Matsuda, Youichirou Higashi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1234 - 1234

Published: Sept. 29, 2024

There is a high demand for the development of drugs against Alzheimer’s disease (AD), which related to misfolding and aggregation Amyloid-β (Aβ), due increasing number patients with AD. In our present study, we aimed assess inhibitory effect various synthetic YS-peptides on Aβ25-35 identify an applicable peptide clinical use AD treatment prevention. Suppression aggregate resolution activities were evaluated using Thioflavin T assay scanning electron microscopy (SEM). Structure–activity relationship studies revealed that YS-RD11 (RETLVYLTHLD) YS-RE16 (RETLVYLTHLDYDDTE) showed suppression aggregate-resolution activities. The phagocytosis in microglial cells (BV-2 cells) demonstrated activated phagocytic ability microglia. Aβ25-35-induced mouse model, prevented improved deficits short-term memory. conclusion, suitable candidate therapeutic drug uses strategy similar used antibodies.

Language: Английский

Alterations in the inflammatory homeostasis of aging‐related cardiac dysfunction and Alzheimer's diseases DOI Open Access
Siyuan Huang, Jeremiah Nunez,

Dai Lan Toresco

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 6, 2025

Alzheimer's disease (AD) is well known among the elderly and has a profound impact on both patients their families. Increasing research indicates that AD systemic disease, with strong connection to cardiovascular disease. They share common genetic factors, such as mutations in presenilin (PS1 PS2) apolipoprotein E (APOE) genes. Cardiovascular conditions can lead reduced cerebral blood flow increased oxidative stress. These factors contribute accumulation of Aβ plaques formation abnormal tau protein tangles, which are key pathological features AD. Additionally, deposits responses have been observed cardiomyocytes peripheral tissues. The toxic deposition intensifies damage microvascular structure associated blood-brain barrier disruption initiation neuroinflammation, may accelerate onset neurocognitive deficits dysfunction. Thus, we discuss main mechanisms linking cardiac dysfunction enhance our understanding these conditions. Ultimately, insights into brain-heart axis help us develop effective treatment strategies future.

Language: Английский

Citations

0
Mitochondrial connection to Alzheimer's disease and heart failure DOI Creative Commons

Anupriya Sinha,

Natasha Jaiswal, Pooja Jadiya

et al.

Current Opinion in Physiology, Journal Year: 2025, Volume and Issue: unknown, P. 100830 - 100830

Published: May 1, 2025

Language: Английский

Citations

0
The causative role of amyloidosis in the cardiac complications of Alzheimer's disease: a comprehensive systematic review DOI Creative Commons
Samuel Parker, Andrew F. James, Svetlana Mastitskaya

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Abstract Alzheimer's disease (AD), the leading cause of dementia, is characterised by cerebral amyloid‐beta (Aβ) and tau deposition, impairing cognition. While cardiovascular diseases exacerbate AD, reverse association underappreciated. This systematic review examined clinical experimental studies that explored cardiogenic dementia hypothesis mechanisms which amyloidosis in AD contributes to complications. A PubMed, Ovid Embase/Medline, CINAHL conducted August 2024 identified 252 meeting selection criteria. Evidence links hypoperfusion from cardiac arrest, heart failure, or orthostatic hypotension pathology, while atherosclerosis hypertension drive neurodegeneration amyloidosis. Vascular scoring tools, such as Framingham Risk Score, may predict an individual's risk cognitive impairment. Cardiac correlated with ECG abnormalities, aortic valve calcification, cardiomyopathy atrial fibrillation. Aβ peptides AD‐related genes fibrosis, negative inotropy rate changes, reduce nitric oxide‐mediated vasodilatation, increase oxidative stress. Preclinical revealed β‐secretase impacts repolarisation interfering delayed rectifier current, although evidence for arrhythmogenesis remains conflicting. autonomic dysregulation, particularly parasympathetic dysfunction, predisposes arrhythmias. Additionally, hypercortisolaemia observed has been associated increased arterial stiffness. Diminished melatonin levels were also linked endothelial mitochondrial dysfunction. enhances our understanding how amyloidosis, endocrinopathy contribute complications paving way research into targeted therapies. image

Language: Английский

Citations

0
Similar normalizing effect of HSP70 and YB-1 stress proteins on the brain transcription of a mouse model of Alzheimer’s disease DOI

Н. В. Бобкова,

Lyubov N. Chuvakova, С. В. Кононова

et al.

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

Published: May 6, 2025

Abstract Previously, we demonstrated therapeutic effects of intranasal administration human HSP70 and YB-1 proteins in various models AD including olfactory bulbectomized (OBX) mice. Herein, investigated the effect these two stress on transcription hippocampus cortex OBX In spite different structure both frequently caused pronounced normalizing changes same genes. Thus, genes that normalized their expression due to action recHSP70 or recYB-1 coincide by 61%. More than 60% common target exhibited complete restoration a pattern control sham-operated Notably, number with altered after was twice as high cortex. brain mice application led normalization many related pathogenesis participated metabolism Aβ tau proteins. Importantly, also include loci involved ribosome biogenesis, well responsible for neurotransmitter transport, cognition, apoptosis, mitochondria functions protection from oxidative stress. A significant positive all six cell types studied most observed astrocytes. Besides AD-related genes, several implicated development major depression other neurodegenerative diseases.

Language: Английский

Citations

0
Investigating the Interplay between Cardiovascular and Neurodegenerative Disease DOI Creative Commons

J. Cousineau,

Aimee Maria Dawe,

Melanie Alpaugh

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 764 - 764

Published: Sept. 26, 2024

Neurological diseases, including neurodegenerative diseases (NDDs), are the primary cause of disability worldwide and second leading death. The chronic nature these conditions lack disease-modifying therapies highlight urgent need for developing effective therapies. To accomplish this, models NDDs required to increase our understanding underlying pathophysiology evaluating treatment efficacy. Traditionally, have focused on central nervous system (CNS). However, evidence points a relationship between systemic factors development NDDs. Cardiovascular disease related risk been shown modify cerebral vasculature Alzheimer’s disease. These findings, combined with reports changes vascular density blood–brain barrier integrity in other NDDs, such as Huntington’s Parkinson’s disease, suggest that cardiovascular health may be predictive brain function. evaluate we explore disruptions circulatory murine CNS summarize combining disruption In this study, aim neurodegeneration interactions across multiple states utility model systems.

Language: Английский

Citations

3
An 11-mer Synthetic Peptide Suppressing Aggregation of Aβ25-35 and Resolving Its Aggregated Form Improves Test Performance in an Aβ25-35-Induced Alzheimer’s Mouse Model DOI Creative Commons
Rina Nakamura, Akira Matsuda, Youichirou Higashi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1234 - 1234

Published: Sept. 29, 2024

There is a high demand for the development of drugs against Alzheimer’s disease (AD), which related to misfolding and aggregation Amyloid-β (Aβ), due increasing number patients with AD. In our present study, we aimed assess inhibitory effect various synthetic YS-peptides on Aβ25-35 identify an applicable peptide clinical use AD treatment prevention. Suppression aggregate resolution activities were evaluated using Thioflavin T assay scanning electron microscopy (SEM). Structure–activity relationship studies revealed that YS-RD11 (RETLVYLTHLD) YS-RE16 (RETLVYLTHLDYDDTE) showed suppression aggregate-resolution activities. The phagocytosis in microglial cells (BV-2 cells) demonstrated activated phagocytic ability microglia. Aβ25-35-induced mouse model, prevented improved deficits short-term memory. conclusion, suitable candidate therapeutic drug uses strategy similar used antibodies.

Language: Английский

Citations

0