Repercussions of microglial efferocytosis on neurodegeneration in Alzheimer’s Disease (AD): a double-edged sword and perplexing factor warranting scrutiny in AD research DOI Creative Commons
Sri Harsha Kanuri

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

Published: July 3, 2024

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative characterized by the accumulation of amyloid beta (Aβ) and tau aggregates within neuronal milieu. To prevent their neurotoxicity, these pathological will be cleared from environment extracellular, intracellular, excretory mechanisms. As compensatory mechanisms become overwhelmed, left-behind instigate loss via varied downstream signaling events. result, neurons undergo cell death through apoptosis necrosis leading to cellular debris. Timely clearance this debris critical, otherwise it can further potentiate perpetuating pro-inflammatory environment. Results Microglial cells migrate engulf dead process known as canonical efferocytosis. On other hand, normal living microglial extracellular exposure phosphatidyl serine (PS) under influence Aβ non-canonical Canonical efferocytosis should predominant with absence during physiological conditions. Upregulation cytokines, chemokines in AD creates fertile ground for amplification parallel The preponderance over pathways leads exuberant stressed along neurons, thereby exacerbated loss, brain tissue thinning severe cognitive disturbances AD. Conclusions Research efforts directed understanding factors that fine-tune balance between processes. Novel therapeutic strategies reinforce beneficial improving repair, healing, regeneration

Language: Английский

Mitochondria in Alzheimer’s Disease Pathogenesis DOI Creative Commons
Allison B. Reiss,

Shelly Gulkarov,

Benna Jacob

et al.

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 196 - 196

Published: Jan. 30, 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years above. It causes dementia with memory loss deterioration in thinking language skills. AD characterized by specific pathology resulting from the accumulation brain of extracellular plaques amyloid-β intracellular tangles phosphorylated tau. The importance mitochondrial dysfunction pathogenesis, while previously underrecognized, now more appreciated. Mitochondria are an essential organelle involved cellular bioenergetics signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, trafficking, fission, fusion dysregulated brain. Excess fission fragmentation yield mitochondria low energy production. Reduced glucose metabolism also observed hypometabolic state, particularly temporo-parietal regions. This review addresses multiple ways which abnormal structure function contribute to AD. Disruption electron transport chain ATP production neurotoxic because cells have disproportionately high demands. In addition, oxidative stress, extremely damaging nerve cells, rises dramatically dyshomeostasis. Restoring health may be viable approach treatment.

Language: Английский

Citations

26
Evolving therapeutic interventions for the management and treatment of Alzheimer’s disease DOI
Faizan Ahmad, Anik Karan, Rashi Sharma

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102229 - 102229

Published: Feb. 15, 2024

Language: Английский

Citations

16
Alzheimer’s Disease as Type 3 Diabetes: Understanding the Link and Implications DOI Open Access
Mateusz Kciuk, Weronika Kruczkowska, Julia Gałęziewska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11955 - 11955

Published: Nov. 7, 2024

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.

Language: Английский

Citations

12
Multi‐Targeting Phytochemicals for Alzheimer's Disease DOI Open Access

R. Bhattacharya,

Raghuraj Singh,

Archna Panghal

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Alzheimer's disease (AD) is a type of neurodegenerative illness in which β-amyloid (Aβ) and tau protein accumulate neurons the form tangles. The pathophysiological pathway AD consists Aβ-amyloid peptides, proteins, oxidative stress increased neuro-inflammatory response. Food Drug Administration United States has authorized various drugs for effective treatment AD, include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, aducanumab. major disadvantage these that they only provide "symptomatic" relief. They are most early stages or mild to moderate cases disease, but not suitable long-term use. Besides conventional therapies, phytochemicals have potential stop progression AD. According research, use against gained attention due their potent anti-inflammatory, antioxidant, anti-hyperphosphorylation protein, metal chelation, anti-amyloid properties. This study seeks an up-to-date compilation current promising breakthroughs therapy using phytochemicals. It could be concluded light serve as However, more mechanistic investigations needed determine clinical implications treatment.

Language: Английский

Citations

1
Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases DOI Creative Commons
Nidhi Puranik, Minseok Song

Neurology International, Journal Year: 2025, Volume and Issue: 17(2), P. 26 - 26

Published: Feb. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Language: Английский

Citations

1
Design of Multi-Target drugs of HDACs and other Anti-Alzheimer related Targets: Current strategies and future prospects in Alzheimer’s diseases therapy DOI
Osama M. Soltan,

Kamal S. Abdelrahman,

Amr K. A. Bass

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 151, P. 107651 - 107651

Published: July 15, 2024

Language: Английский

Citations

6
Neolignans in Magnolia officinalis as natural anti-Alzheimer’s disease agents: A systematic review DOI
Na Li,

Yuanyuan Liang,

Lijuan Zhang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102398 - 102398

Published: June 30, 2024

Language: Английский

Citations

5
Exploring the Mechanisms and Therapeutic Approaches of Mitochondrial Dysfunction in Alzheimer’s Disease: An Educational Literature Review DOI Creative Commons

Mostafa Hossam El Din Moawad,

Ibrahim Serag, Ibraheem M. Alkhawaldeh

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Language: Английский

Citations

4
Drugs repurposing in the experimental models of Alzheimer’s disease DOI Creative Commons

Sheer A. Joodi,

Weam W. Ibrahim, Mahmoud M. Khattab

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract The currently approved drugs for Alzheimer’s disease (AD) are only symptomatic treatment in the early stages of but they could not halt neurodegeneration, additionally, safety profile recently developed immunotherapy is a big issue. This review aims to explain importance repurposing technique and strategy develop therapy AD. We illustrated biological alterations pathophysiology AD including amyloid pathology, Tau oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/ β -catenin signaling, autophagy. Additionally, we demonstrated different repurposed experimental models anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant anticancer drugs. Further, showed pipeline FDA have promising therapeutic activity against AD, confirming value elucidate curative Graphical abstract

Language: Английский

Citations

0
Dihydropyrimidines Emerge as Promising Dual‐Acting Inhibitors Targeting Acetylcholinesterase and Monoamine Oxidases for Alzheimer's and Other Neurological Disorders DOI Open Access

Maria Saleem Khan,

Talha Islam,

Muhammad Umer Farooq

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(6)

Published: Feb. 1, 2025

Abstract The pathogenesis of Alzheimer's disease (AD) is multifaceted, and more than one factor deemed responsible for its genesis progression. Hence, the multi‐target approach seems plausible en route to development therapeutics targeting in particular, other neurological disorders, general. Among major factors AD are acetylcholinesterase monoamine oxidase enzymes. Acetylcholine an important neurotransmitter that plays a role processing memory learning. Deficiency this observed patients AD; largely attributed increased expression enzyme (AChE) breakdown acetylcholine neurotransmitter. inhibitors AChE can prevent excessive Monoamine oxidases brain hydrolyzing neurotransmitters such as serotonin dopamine (among others), abnormally rapid hydrolysis these via over‐activation associated with several neurodegenerative disorders including anxiety Parkinson's disease. Herein, we synthesized focused library 1,4‐dihydropyrimidines (40 compounds) using deep eutectic solvent evaluated their potential inhibit cholinesterase (AChE BChE) (MAO A MAO B) Several selective highly potent were identified; silico molecular docking dynamics simulation studies helped rationalize binding site interactions establish useful structure activity relationship. In ADME prediction data identified few could cross blood‐brain barrier, compound was selected vivo estimation LD 50 value toxicity mice, skin allergy test also carried out. All tests established safety profile compound. results encouraging enough further pursue DHPMs promising directed ligands against disorders.

Language: Английский

Citations

0