Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6518 - 6518

Published: March 30, 2023

Alzheimer’s disease is one of the most commonly diagnosed cases senile dementia in world. It an incurable process, often leading to death. This multifactorial, and factor this inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms disease, contributing progression, also directly underlie AD. Although much has been established about processes pathogenesis AD, many aspects remain unexplained. The work devoted particular pathomechanism inflammation its role diagnosis treatment. An in-depth detailed understanding neuroinflammation help development diagnostic methods for early contribute new therapeutic strategies disease.

Language: Английский

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Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2728 - 2728

Published: Sept. 1, 2022

Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent main pathological hallmarks AD brain. Recently, neuroinflammation has been recognized as prominent feature brain substantial evidence suggests that inflammatory response modulates progression. Additionally, dysregulation calcium (Ca2+) homeostasis represents another early factor involved in pathogenesis, intracellular Ca2+ concentration essential to ensure proper cellular neuronal functions. Although growing supports involvement mechanisms neurodegeneration-related processes, scant data are available on its contribution microglia astrocytes functioning, both health throughout continuum. Nevertheless, AD-related aberrant signalling crucially underpinning neuroinflammatory processes that, turn, impact function. In this light, we attempted provide an overview current understanding interactions between glia cells-mediated responses molecular AD.

Language: Английский

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Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 8, 2023

Alzheimer's disease (AD) is a prevalent neurodegenerative characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number AD patients, elucidating underlying mechanisms developing corresponding interventional strategies are necessary. Hypotheses about such as amyloid cascade, Tau hyper-phosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, vascular hypotheses not mutually exclusive, them play certain role in development AD. The cascade hypothesis currently most widely studied; however, other also gaining support. This article summarizes recent evidence regarding major pathological their potential interplay, well strengths weaknesses each implications effective treatments. could stimulate further studies promote more therapeutic

Language: Английский

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Aducanumab—Hope or Disappointment for Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4367 - 4367

Published: Feb. 22, 2023

In June 2021, the world was informed about a new drug for Alzheimer’s disease approved by FDA. Aducanumab (BIIB037, ADU), being monoclonal antibody IgG1, is newest AD treatment. The activity of targeted towards amyloid β, which considered one main causes disease. Clinical trials have revealed time- and dose-dependent Aβ reduction, as well cognition improvement. Biogen, company responsible conducting research introducing to market, presents solution cognitive impairment, but its limitations, costs, side effects are controversial. framework paper focuses on mechanism aducanumab’s action along with positive negative sides therapy. review basis hypothesis that cornerstone therapy, latest information aducanumab, action, possibility use drug.

Language: Английский

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The duality of amyloid-β: its role in normal and Alzheimer’s disease states

Molecular Brain, Journal Year: 2024, Volume and Issue: 17(1)

Published: July 17, 2024

Abstract Alzheimer’s disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of brain. A key characteristic AD accumulation amyloid-beta (Aβ) plaques, which play pivotal roles in progression. These plaques initiate cascade events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial disrupted calcium homeostasis. Aβ also closely associated with other hallmark features AD, underscoring its significance. generated through cleavage amyloid precursor (APP) plays dual role depending on processing pathway. The non-amyloidogenic pathway reduces production has neuroprotective anti-inflammatory effects, whereas amyloidogenic leads to peptides, Aβ40 Aβ42, contribute neurodegeneration toxic effects AD. Understanding multifaceted Aβ, particularly crucial for developing effective therapeutic strategies target metabolism, aggregation, clearance aim mitigating detrimental consequences disease. This review aims explore mechanisms functions under normal abnormal conditions, examining both beneficial effects.

Language: Английский

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Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9067 - 9067

Published: May 22, 2023

Alzheimer’s disease (AD) is a chronic neurodegenerative and the most frequent cause of progressive dementia in senior adults. It characterized by memory loss cognitive impairment secondary to cholinergic dysfunction N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed amyloid-β (Aβ), selective neurodegeneration are anatomopathological hallmarks this disease. The dysregulation calcium may be present all stages AD, it associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, neuroinflammation. Although cytosolic alterations AD not completely elucidated, some calcium-permeable channels, transporters, pumps, receptors have been shown involved at neuronal glial levels. In particular, relationship between glutamatergic NMDA receptor (NMDAR) activity amyloidosis has widely documented. Other mechanisms dyshomeostasis include activation L-type voltage-dependent transient potential ryanodine receptors, among many others. This review aims update calcium-dysregulation discuss targets molecules therapeutic based on their modulation.

Language: Английский

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The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6827 - 6827

Published: April 6, 2023

Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up 120 types of phytocannabinoids present in hemp. Hemp leaves contain large amounts Cannabidiolic acid (CBDA) Tetrahydrocannabinolic (THCA), which acidic variants CBD THC account for the largest proportion CBDA. In recent studies, CBDA exhibited anti-hyperalgesia anti-inflammatory effects. THCA also showed neuroprotective effects that may be beneficial treating neurodegenerative diseases. can penetrate blood-brain barrier (BBB) affect central nervous system. The purpose this study was determine whether ameliorate Alzheimer's disease (AD)-like features vitro vivo. effect evaluated Aβ1-42-treated mouse model. We observed mice had more hippocampal Aβ p-tau levels, pathological markers AD, loss cognitive function compared with PBS-treated mice. However, CBDA- THCA-treated decreased superior addition, lowered alleviated calcium dyshomeostasis, primary neurons. Our results suggest have anti-AD mitigate memory resilience increased Ca2+, Aβ, levels. Together, useful therapeutic agents AD.

Language: Английский

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Parvalbumin: A Major Fish Allergen and a Forensically Relevant Marker

Genes, Journal Year: 2023, Volume and Issue: 14(1), P. 223 - 223

Published: Jan. 14, 2023

Parvalbumins (PVALBs) are low molecular weight calcium-binding proteins. In addition to their role in many biological processes, PVALBs play an important regulating Ca2+ switching muscles with fast-twitch fibres processes. The PVALB gene family is divided into two types, alpha (α) and beta (β), the β further beta1 (β1) beta2 (β2), carrying traces of whole genome duplication. A large variety commonly consumed fish species contain proteins which known cause allergies. More than 95% all fish-induced food allergies caused by authentication has become increasingly as seafood industry continues grow growth brings it cases fraud. Since plays initiation allergic reactions, been used for decades develop alternate assays identification. brief review significance genes presented this article, covers evolutionary diversity, properties, potential use a forensic marker.

Language: Английский

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Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer’s disease

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: June 9, 2023

The integration of quantitative trait loci (QTL) with disease genome-wide association studies (GWAS) has proven successful at prioritizing candidate genes disease-associated loci. QTL mapping mainly been focused on multi-tissue expression or plasma protein (pQTL). Here we generated the largest-to-date cerebrospinal fluid (CSF) pQTL atlas by analyzing 7,028 proteins in 3,107 samples. We identified 3,373 independent study-wide associations for 1,961 proteins, including 2,448 novel pQTLs which 1,585 are unique to CSF, demonstrating genetic regulation CSF proteome. In addition established chr6p22.2-21.32 HLA region, pleiotropic regions chr3q28 near

Language: Английский

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Reduced Prevalence of Dementia in Patients Prescribed Tacrolimus, Sirolimus, or Cyclosporine

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(2), P. 585 - 597

Published: Aug. 8, 2023

Evidence suggests patients prescribed calcineurin inhibitors (CNIs) have a reduced prevalence of dementia, including Alzheimer's disease (AD); however, this result has never been replicated in large cohort and the involved mechanism(s) site action (central versus periphery) remain unclear.We aim to determine if prescription CNIs is associated with AD, large, diverse patient population. Furthermore, we gain insight into for reduce dementia prevalence.Electronic health records (EHRs) from tacrolimus, cyclosporine, or sirolimus were analyzed compare prevalence, odds, hazard ratios related diagnoses among cohorts. EHRs random, heterogeneous population same network obtained generate general population-like control.All drugs examined compared control. There no differences upon comparing tacrolimus sirolimus; had relative cyclosporine.Converging mechanisms between likely explain similar Calcineurin inhibition within brain greater probability reducing peripherally-restricted inhibition. Overall, immunosuppressants provide promising therapeutic avenue emphasis on brain-penetrant CNI tacrolimus.

Language: Английский

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