Mechanistic Approach to Immunity and Immunotherapy of Alzheimer’s Disease: A Review DOI

Md. Rubiath Islam,

Md. Afser Rabbi,

Tanbir Hossain

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Alzheimer's disease (AD) is a debilitating neurodegenerative condition characterized by progressive cognitive decline and memory loss, affecting millions of people worldwide. Traditional treatments, such as cholinesterase inhibitors NMDA receptor antagonists, offer limited symptomatic relief without addressing the underlying mechanisms. These limitations have driven development more potent effective therapies. Recent advances in immunotherapy present promising avenues for AD treatment. Immunotherapy strategies, including both active passive approaches, harness immune system to target mitigate AD-related pathology. Active stimulates patient's response produce antibodies against AD-specific antigens, while involves administering preformed or cells that specifically amyloid-β (Aβ) tau proteins. Monoclonal antibodies, aducanumab lecanemab, shown potential reducing Aβ plaques slowing clinical trials, despite challenges related adverse responses need precise targeting. This comprehensive review explores role AD, evaluates current successes immunotherapeutic discusses future directions enhancing treatment efficacy.

Language: Английский

New insights in animal models of neurotoxicity-induced neurodegeneration DOI Creative Commons
Coral Sanfeliu, Clara Bartra, Cristina Suñol

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 8, 2024

The high prevalence of neurodegenerative diseases is an unintended consequence the longevity population, together with lack effective preventive and therapeutic options. There great pressure on preclinical research, both old new models are required to increase pipeline drugs for clinical testing. We review here main neurotoxicity-based animal leading central neurodegeneration. Our focus was studying how changes in neurotransmission neuroinflammation, mainly rodent models, contribute harmful processes linked majority currently use mimic Parkinson's disease (PD) Alzheimer's (AD), which most common conditions older adults. AD age-related dementia, whereas PD movement disorder also cases dementia. Several natural toxins xenobiotic agents induce dopaminergic neurodegeneration can reproduce neuropathological traits PD. literature analysis MPTP, 6-OH-dopamine, rotenone suggested latter as a useful model when specific doses were administrated systemically C57BL/6 mice. Cholinergic modelled toxin scopolamine, screening protective against cognitive decline AD. have been used neuroinflammation-based dementia AD, including lipopolysaccharide (LPS), streptozotocin, monomeric C-reactive protein. bacterial agent LPS makes testing anti-inflammatory therapies halt development severity However, neurotoxin might be more than genetic drug discovery but that not case where they cannot beat developments transgenic mouse models. Overall, we should work using all available either

Language: Английский

Citations

17
A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses DOI Creative Commons
Masaru Tanaka, László Vécsei

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1083 - 1083

Published: May 13, 2024

Welcome to

Language: Английский

Citations

17
A New Strategy for the Regulation of Neuroinflammation: Exosomes Derived from Mesenchymal Stem Cells DOI Creative Commons
Ying Ge, Jingjing Wu, Li Zhang

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Feb. 19, 2024

Abstract Neuroinflammation is an important pathogenesis of neurological diseases and causes a series physiopathological changes, such as abnormal activation glial cells, neuronal degeneration death, disruption the blood‒brain barrier. Therefore, modulating inflammation may be therapeutic tool for treating diseases. Mesenchymal stem cells (MSCs), pluripotent have great potential due to their regenerative ability, immunity, ability regulate inflammation. However, recent studies shown that MSC-derived exosomes (MSC-Exos) play major role in this process key neuroprotection by regulating neuroglia. This review summarizes progress made neuroinflammation focusing on mechanisms which MSC-Exos are involved regulation through signaling pathways TLR, NF-κB, MAPK, STAT, NLRP3 provide some references subsequent research therapy. Graphical Exosomes derived from MSCs exhibit neuroprotective effects mitigating triggered cells.

Language: Английский

Citations

16
Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier DOI Creative Commons

Pushpa Tryphena Kamatham,

Rashi K. Shukla, Dharmendra Kumar Khatri

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102481 - 102481

Published: Sept. 3, 2024

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.

Language: Английский

Citations

13
Targeting the molecular web of Alzheimer’s disease: unveiling pathways for effective pharmacotherapy DOI Creative Commons
Devika Jadhav, Nikita Saraswat,

Neeraj S. Vyawahare

et al.

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Journal Year: 2024, Volume and Issue: 60(1)

Published: Jan. 11, 2024

Abstract Introduction Alzheimer’s disease is a neurocognitive disorder that affects elderly people by slowly impaired cognition, dementia, and gets worse with age. It impacts the quality of life. Clinically, it distinguished transition from episodic memory to gradual reduction in cognitive ability leading dysfunction. Neurofibrillary tangles amyloid plaques are unique structures thought have role pathogenesis Alzheimer's disease. In this review, we focus our attention on risk factors, pathophysiology, etiology, epidemiology, stages, diagnosis, treatment, mechanisms, pathways, ongoing clinical trials data risks potentially associated development Short summary This review aims extrapolate information about Preliminary research was done selecting reviews PubMed, Elsevier, Google open-access publications using keywords like “Alzheimer, neurodegenerative, memory, β, mechanism action, pathways”. Conclusion Here show discussion interpretation several signaling pathways such as β plaque cleavage, Metal ion hypothesis, degradation, initiation amyloidogenic non-amyloidogenic pathway, oxidative stress Metabolic syndrome, insulin resistance tau phosphorylation apolipoprotein- cholesterol, neurofibrillary accumulation, which significant for better understanding progression. On studying trials, found current drugs being tested crenezumab, gantenerumab sodium oligonucleotide. Graphical

Language: Английский

Citations

8
DDQ anti-aging properties expressed with improved mitophagy in mutant tau HT22 neuronal cells DOI Creative Commons
Jangampalli Adi Pradeepkiran,

Priyanka Rawat,

Arubala P. Reddy

et al.

Mitochondrion, Journal Year: 2024, Volume and Issue: 75, P. 101843 - 101843

Published: Jan. 19, 2024

Language: Английский

Citations

8
Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration DOI
Riya Thapa, Asif Ahmad Bhat, Moyad Shahwan

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

Citations

8
From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders DOI Creative Commons
Elisa Duranti, Chiara Villa

Biology, Journal Year: 2024, Volume and Issue: 13(9), P. 719 - 719

Published: Sept. 12, 2024

Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's (PD), primarily affect the central nervous system, leading to progressive neuronal loss motor cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe wasting as result of neuron degeneration, well alterations gene expression, protein aggregation, oxidative stress. Muscle atrophy mitochondrial dysfunction are observed AD, which may exacerbate decline due systemic metabolic dysregulation. PD patients exhibit fiber atrophy, altered composition, α-synuclein aggregation within cells, contributing symptoms progression. Systemic inflammation impaired degradation pathways common among disorders, highlighting key player Understanding muscle-related changes offers potential therapeutic avenues, such targeting function, reducing inflammation, promoting regeneration with exercise pharmacological interventions. This review emphasizes importance considering an integrative approach neurodegenerative research, both peripheral pathological mechanisms, order develop more effective treatments improve patient outcomes.

Language: Английский

Citations

8
Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer's disease DOI Creative Commons
Allison Carles,

Aline Freyssin,

Sarra Guehairia

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 6, 2025

Fluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25–35] peptide (Aβ25–35)-induced neurotoxicity in mice, pharmacological model of Alzheimer's disease (AD) with high predictive value for drug discovery. Here, as infusion is likely to better reflect bioavailability due the interspecies pharmacokinetics variation, we analyzed efficacy FENM after chronic subcutaneous (SC) infusion, comparison IP injections two AD mouse models, Aβ25–35-injected mice and transgenic APPswe/PSEN1∂E9 (APP/PS1) line. In Aβ25–35-treated was infused at 0.03–0.3 mg/kg/day during one week Aβ25–35 injection. For comparison, MEM were administered daily mg/kg. 10-month-old APP/PS1 four weeks by 0.3 mg/kg or SC 0.1 mg/kg/day. Memory deficits, spatial working memory recognition memory, analysed. Markers neuroinflammation, apoptosis, oxidative stress, amyloid burden quantified. synaptic plasticity such PSD-95 GluN2A/B/D subunits expression hippocampus homogenates synaptosomes quantified long-term potentiation (LTP) hippocampal slices analysed mice. Deficits spontaneous alternation object all doses tested. Similar effects observed treatments. Animals showed prevention Aβ25–35-induced stress apoptosis. restored alterations synaptosomal PSD-95, GluN2A P-GluN2B levels. GluN2D levels unchanged whatever treatment. alleviated increases Aβ1-40/Aβ1-42 LTP alteration. These data confirmed neuroprotective potential models AD, superiority MEM, that can be efficiently chronically.

Language: Английский

Citations

1
Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease DOI Creative Commons
Yashumati Ratan, Aishwarya Rajput, Ashutosh Pareek

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 73 - 73

Published: Jan. 5, 2024

Parkinson’s disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over decades that explain pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to intricate pathophysiology PD and poorly understood molecular mechanism. To address these challenges comprehensively, a thorough model imperative nuanced understanding PD’s underlying pathogenic mechanisms. review offers detailed analysis current state knowledge regarding mechanisms with particular emphasis on roles played gene-based factors in disease’s development progression. study includes an extensive discussion proteins mutations primary genes linked including α-synuclein, GBA1, LRRK2, VPS35, PINK1, DJ-1, Parkin. Further, this explores plausible DAergic neural loss, non-motor non-dopaminergic pathologies, risk associated The present will encourage related research fields understand better analyze status biochemical might contribute design efficacious safe treatment strategies future endeavors.

Language: Английский

Citations

7