Alterations in the <em>amyloid protein precursor</em>, <em>α-secretase</em>, <em>β-secretase</em>, <em>presenilins</em> and <em>tau protein</em> Genes in the CA3 Area of the Hippocampus in a 2-Year Ischemic Model of Alzheimer’s Disease DOI Open Access
Stanisław J. Czuczwar, Janusz Kocki, Barbara Miziak

et al.

Published: Sept. 30, 2023

Understanding the phenomena underlying non-selective susceptibility to ischemia of py-ramidal neurons in CA3 area hippocampus is important from point view elu-cidating mechanisms memory loss and development post-ischemic dementia. We used an ischemic model Alzheimer's disease study changes amyloid protein precursor gene expression, its cleavage enzymes tau af-ter a 10-minute brain with 12, 18, 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that expression all genes contribute pro-duction was dysregulated within 2 years after ischemia. The above control values at times study. &alpha;-secretase also exceeded throughout In contrast, &beta;-secretase reaching maximum increase 12 months ischemia, below 18 again 24 Presenilin 1 significantly elevated follow-up period, peak both occurring This suggests studied are involved non-amyloidogenic processing precursor. Also, observation present is-chemia. Data indicate episode long-term survival causes damage death pyramidal manner dependent on modified protein. Thus defining new mechanism neuronal addition modification is-chemia useful identifying disease.

Language: Английский

Amyloid-β and heart failure in Alzheimer’s disease: the new vistas DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 4, 2025

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% all types. AD neuropathology due to progressive deposition extracellular amyloid-beta (A β ) peptide intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while protein neurofibrillary tangles (NFTs). Both plaques NFTs are hallmarks neuropathology. fundamental mechanism involved in pathogenesis still elusive, although more conceivable theory. Aβ-induced neurodegeneration associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), mitochondrial dysfunction contribute development cognitive impairment dementia. Of note, not only originated from brain but also produced peripherally and, via blood–brain barrier (BBB), can accumulate result AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), heart failure (HF) regarded possible risk factors for other types dementia, vascular HF-induced chronic cerebral hypoperfusion, inflammation induce progression Interestingly, a systemic causes which turn affects peripheral organs, including heart. through deranged BBB be transported into circulation heart, leading HF. These findings suggest close relationship between However, exact AD-induced HF fully elucidated. Therefore, this review aims discuss link regarding potential role

Language: Английский

Citations

4
Navigating the Maze of Alzheimer’s disease by exploring BACE1: Discovery, current scenario, and future prospects DOI

Faiza Iram,

Mohammad Shahid, Jaoud Ansari

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102342 - 102342

Published: May 16, 2024

Language: Английский

Citations

7
Apoptosis, Autophagy, and Mitophagy Genes in the CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival DOI Creative Commons
Ryszard Pluta, Anna Bogucka‐Kocka, Jacek Bogucki

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 99(4), P. 1375 - 1383

Published: May 17, 2024

Background: Currently, no evidence exists on the expression of apoptosis (CASP3), autophagy (BECN1), and mitophagy (BNIP3) genes in CA3 area after ischemia with long-term survival. Objective: The goal paper was to study changes above period 6–24 months. Methods: In this study, using quantitative RT-PCR, we present associated neuronal death a rat ischemic model Alzheimer’s disease. Results: First time, demonstrated overexpression CASP3 gene survival ranging from 0.5 2 years. Overexpression accompanied by decrease activity level BECN1 BNIP3 over year. Then, during 1-2 years, increased significantly coincided an increase expression. However, variable, at 1 years below control values 1.5 post-ischemia. Conclusions: Our observations suggest that induces through activation caspase 3 cooperation pro-apoptotic BNIP3. This also suggests regulates caspase-independent pyramidal Thus, caspase-dependent -independent cells occur post-ischemia area. data new role regulation post-ischemic CA3. involvement together

Language: Английский

Citations

6
Ischemia-Reperfusion Programming of Alzheimer’s Disease-Related Genes—A New Perspective on Brain Neurodegeneration after Cardiac Arrest DOI Open Access
Ryszard Pluta, Stanisław J. Czuczwar

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1291 - 1291

Published: Jan. 20, 2024

The article presents the latest data on pathological changes after cerebral ischemia caused by cardiac arrest. include amyloid accumulation, tau protein modification, neurodegenerative and cognitive changes, gene associated with Alzheimer’s disease. We present dysregulation of genes related to metabolism precursor, protein, autophagy, mitophagy, apoptosis, transport genes. report that neuronal death due arrest may be dependent independent caspase. Moreover, modified has been demonstrated. Finally, results clearly indicate in expression presented play an important role acute secondary brain damage development post-ischemic neurodegeneration disease phenotype. above a potential therapeutic target for therapy Overall, studies show studied represent attractive targets new therapies minimize ischemic injury neurological dysfunction. Additionally, amyloid-related modification are useful identifying mechanisms Cardiac illustrates progressive, time- area-specific neuropathology responsible processing precursor occurrence symptoms dementia such as those occurring patients By carefully examining common genetic processes involved these two diseases, help unravel phenomena lead future research or directions.

Language: Английский

Citations

5
Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer’s disease-associated metabolites DOI Creative Commons
Brendan K. Ball, Madison K. Kuhn,

Rebecca M. Fleeman Bechtel

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 3, 2024

Abstract Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer’s disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses primary neurons to potentially circulating, blood–brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine protective detrimental properties AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic aminoadipic sorbitol, retinol, tryptophan, niacinamide) stimulated mouse neuron cultures each metabolite before quantifying cytokine secretion via Luminex. employed unsupervised clustering, inferential statistics, partial least squares discriminant analysis identify relationships between concentration disease-associations metabolites. MCP-1, monocyte recruitment, differentially abundant by T2D. also IL-9, that promotes mast cell growth, be Indeed, cytokines, such MCP-1 released from response BBB-permeable may contribute development downstream effects neuroinflammation.

Language: Английский

Citations

5
Trans- and Cis-Phosphorylated Tau Protein: New Pieces of the Puzzle in the Development of Neurofibrillary Tangles in Post-Ischemic Brain Neurodegeneration of the Alzheimer’s Disease-like Type DOI Open Access
Ryszard Pluta, Stanisław J. Czuczwar

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3091 - 3091

Published: March 7, 2024

Recent evidence indicates that experimental brain ischemia leads to dementia with an Alzheimer's disease-like type phenotype and genotype. Based on the above evidence, it was hypothesized may contribute development of disease. Brain disease are two diseases characterized by similar changes in hippocampus closely related memory impairment. Following animals humans, presence amyloid plaques extracellular space intracellular neurofibrillary tangles revealed. The phenomenon tau protein hyperphosphorylation is a pathological feature both post-ischemic injury In disease, phosphorylated Thr231 motif has distinct trans cis conformations primary site phosphorylation pre-entanglement cascade acts as early precursor neuropathology form tangles. latest publication, we present mechanism formation after established trans- cis-phosphorylation protein, which ultimately influences tauopathy.

Language: Английский

Citations

4
A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model DOI
Ryszard Pluta

Current Alzheimer Research, Journal Year: 2024, Volume and Issue: 21(3), P. 166 - 182

Published: March 1, 2024

Alzheimer's disease (AD) is the frequent form of dementia in world. Despite over 100 years research into causes AD, including amyloid and tau protein, has stalled not led to any conclusions. Moreover, numerous projects aimed at finding a cure for AD have also failed achieve breakthrough. Thus, failure anti-amyloid anti-tau protein therapy treat significantly influenced way we began think about etiology disease. This situation prompted group researchers focus on ischemic brain episodes, which, like mostly present alterations hippocampus. In this context, it been proposed that cerebral incidents may play major role promoting neurodegeneration AD. review, summarized experimental clinical conducted several episodes development Studies shown changes typical course post-ischemia, i.e., progressive hippocampal atrophy, increased production, modification protein. post-ischemic brain, diffuse senile plaques neurofibrillary tangles characteristic were revealed. The above data evidently showed after ischemia, there are modifications folding, leading massive neuronal death damage network, which triggers with phenotype.

Language: Английский

Citations

4
Gut-Brain Axis and a Systematic Approach to Alzheimer’s Disease Therapies DOI Creative Commons
Jinhe Li,

Huilin Mou,

Ranran Yao

et al.

Brain Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Alzheimer’s disease (AD) is a critical issue that affects both the quality of life families and public health. Despite years research, single-target therapies for AD remain limited. This primarily because complex multifaceted pathological mechanisms underlying AD. Recent findings involvement gut microbiome dysbiosis in pathogenesis have offered novel insights, emphasizing need holistic approaches. As progresses, microbiota alterations contribute to metabolic immune imbalances, sparking peripheral inflammation. Consequently, there heightened infiltration cells into brain, thus exacerbating neuroinflammation cognitive decline. Notably, drug developments targeting this mechanism witnessed substantial advancements, presenting systematic treatment approaches patients. Furthermore, plays pivotal role many other diseases their associated impairments. The gut-brain axis, bidirectional communication network, therefore holds significant promise as well broader impairment solutions, beyond those based on amyloid-beta tau theories.

Language: Английский

Citations

0
Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years DOI Creative Commons
Stanisław J. Czuczwar, Janusz Kocki, Barbara Miziak

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 98(1), P. 151 - 161

Published: Feb. 20, 2024

Background: Understanding the phenomena underlying non-selective susceptibility to ischemia of pyramidal neurons in CA3 is important from point view elucidating mechanisms memory loss and development dementia. Objective: The aim study was investigate changes genes expression amyloid precursor protein, its cleaving enzymes tau protein post-ischemia with survival 12–24 months. Methods: We used an ischemic model Alzheimer’s disease above using RT-PCR protocol. Results: gene control values at all times post-ischemia. α-secretase also exceeded β-secretase increased 12 24 months post-ischemia, 18 below values. Presenilin 1 2 significantly elevated Also, throughout observation period, peak present Conclusions: suggests that studied are involved non-amyloidogenic processing protein. Additionally data indicate brain long-term causes damage death area hippocampus a modified protein-dependent manner. Thus defining new mechanism neuronal In addition modification after useful identifying occurring disease.

Language: Английский

Citations

3
Current and further outlook on the protective potential of Antrodia camphorata against neurological disorders DOI Creative Commons
Weiling Li, Pin Wan, Jialu Qiao

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 17, 2024

Prevalent neurological disorders such as Alzheimer's disease, Parkinson's and stroke are increasingly becoming a global burden society ages. It is well-known that degeneration loss of neurons the fundamental underlying processes, but there still no effective therapies for these diseases. In recent years, plenty studies have focused on pharmacology feasibility natural products new strategies development drugs target disorders.

Language: Английский

Citations

3