Amyloid Beta in Aging and Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 12924 - 12924

Published: Oct. 26, 2022

Alzheimer’s disease (AD), is a progressive neurodegenerative that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs two forms, early onset familial late-onset sporadic; genetic mutations PS1, PS2, APP genes cause AD, combination of lifestyle, environment factors causes the sporadic form disease. However, accelerated progression noticed patients with AD. Disease-causing pathological changes are synaptic damage, mitochondrial structural functional changes, addition to increased production accumulation phosphorylated tau (p-tau), amyloid beta (Aβ) affected brain regions patients. Aβ peptide derived from precursor protein (APP) by proteolytic cleavage gamma secretases. glycoprotein plays significant role maintaining neuronal homeostasis like signaling, development, intracellular transport. reported have both protective toxic effects neurons. The purpose our article summarize recent developments its association synapses, mitochondria, microglia, astrocytes, interaction p-tau. Our also covers therapeutic strategies reduce toxicities discusses reasons for failures therapeutics.

Language: Английский

---

Tumor Necrosis Factor and Interleukin-1β Modulate Synaptic Plasticity during Neuroinflammation

Neural Plasticity, Journal Year: 2018, Volume and Issue: 2018, P. 1 - 12

Published: Jan. 1, 2018

Cytokines are constitutively released in the healthy brain by resident myeloid cells to keep proper synaptic plasticity, either form of Hebbian plasticity or homeostatic plasticity. However, when cytokines dramatically increase, establishing a status neuroinflammation, action such molecules remarkably interferes with circuits learning and cognition contributes excitotoxicity neurodegeneration. Among others, interleukin-1 β (IL-1 ) tumor necrosis factor (TNF) best studied proinflammatory both physiological pathological conditions have been invariably associated long-term potentiation (LTP) (Hebbian plasticity) scaling (homeostatic plasticity), respectively. Multiple sclerosis (MS) is prototypical neuroinflammatory disease, which inflammation triggers excitotoxic mechanisms contributing IL- TNF increased MS patients contribute induce changes occurring its animal model, experimental autoimmune encephalomyelitis (EAE). This review will introduce discuss current evidence role IL-1 regulation strength at levels, particular speculating on their involvement observed EAE brain.

Language: Английский

---

A Close Look at BACE1 Inhibitors for Alzheimer’s Disease Treatment

CNS Drugs, Journal Year: 2019, Volume and Issue: 33(3), P. 251 - 263

Published: March 1, 2019

Language: Английский

---

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Sept. 24, 2022

Abstract ApoE is the major lipid and cholesterol carrier in CNS. There are three human polymorphisms, apoE2, apoE3, apoE4, genetic expression of APOE4 one most influential risk factors for development late-onset Alzheimer's disease (AD). Neuroinflammation has become third hallmark AD, together with Amyloid-β plaques neurofibrillary tangles hyperphosphorylated aggregated tau protein. This review aims to broadly extensively describe differential aspects concerning apoE. Starting from evolution apoE how APOE's single-nucleotide polymorphisms affect its structure, function, involvement during health disease. reflects on impact critical AD pathology, such as neuroinflammatory response, particularly effect APOE astrocytic microglial function dynamics, synaptic amyloid-β load, autophagy, cell–cell communication. We discuss affecting pathology combined genotype, sex, age, diet, physical exercise, current therapies clinical trials field. The genotype other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, multiple also addressed. Therefore, this gathers relevant findings related up date implications CNS pathologies provide a deeper understanding knowledge

Language: Английский

---

Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

---