Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders DOI Creative Commons

Qing Qiu,

Mengting Yang,

Danfeng Gong

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1258 - 1276

Published: June 3, 2024

The central nervous system, information integration center of the body, is mainly composed neurons and glial cells. neuron one most basic important structural functional units with sensory stimulation excitation conduction functions. Astrocytes microglia belong to cell family, which main source cytokines represents defense system system. Nerve cells undergo neurotransmission or gliotransmission, regulates neuronal activity via ion channels, receptors, transporters expressed on nerve membranes. Ion large transmembrane proteins, play crucial roles in maintaining homeostasis. These channels are also for control membrane potential secretion neurotransmitters. A variety cellular functions life activities, including regulation generation excitation, occurrence receptor potential, heart pulsation, smooth muscle peristalsis, skeletal contraction, hormone secretion, closely related associated passive transport. Two types potassium calcium various neurological disorders, Alzheimer’s disease, Parkinson’s epilepsy. Accordingly, drugs that can affect these have been explored deeply provide new directions treatment disorders. In this review, we focus different their involvement disorders such as depression, epilepsy, autism, rare We describe several clinical target could be used treat concluded there few improve pathology diseases by acting ions. Although a novel ion-channel-specific modulators discovered, meaningful therapies largely not yet realized. lack target-specific drugs, requirement cross blood–brain barrier, exact underlying mechanisms all need further attention. This review aims explain urgent problems research progress comprehensive aiming arouse community’s interest development channel-targeting identification therapeutic targets increase cure rate reduce adverse reactions other systems.

Language: Английский

Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues DOI Creative Commons

Niyatee Samudra,

Courtney Lane‐Donovan, Lawren VandeVrede

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(12)

Published: June 14, 2023

Tauopathies are disorders associated with tau protein dysfunction and insoluble accumulation in the brain at autopsy. Multiple lines of evidence from human disease, as well nonclinical translational models, suggest that has a central pathologic role these disorders, historically thought to be primarily related gain toxic function. However, number tau-targeting therapies various mechanisms action have shown little promise clinical trials different tauopathies. We review what is known about biology, genetics, therapeutic been tested date. discuss possible reasons for failures therapies, such use imperfect models do not predict effects drug development; heterogeneity pathologies which may lead variable responses therapy; ineffective mechanisms, targeting wrong species or epitope. Innovative approaches can help address some difficulties plagued our field's development thus far. Despite limited success date, we continue refine understanding tau's pathogenic mechanism(s) neurodegenerative diseases, remain optimistic will eventually play treatment

Language: Английский

Citations

51
NF-κB as an Inducible Regulator of Inflammation in the Central Nervous System DOI Creative Commons

Sudha Anilkumar,

Elizabeth C. Wright-Jin

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 485 - 485

Published: March 11, 2024

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription family is critical for modulating the immune proinflammatory response throughout body. During resting state, inactive sequestered by IκB in cytoplasm. proteasomal degradation activates NF-κB, mediating its translocation into nucleus to act as a nuclear upregulation genes. Stimuli that initiate activation are diverse but canonically attributed cytokines and chemokines. Downstream effects cell type-specific and, majority cases, result pro-inflammatory cascades. Acting primary responders central nervous system, microglia exhibit upon pathological conditions. Under such circumstances, microglial crosstalk with other types system can induce death, further exacerbating disease pathology. In this review, we will emphasize role triggering neuroinflammation mediated microglia.

Language: Английский

Citations

33
Alzheimer’s disease and its treatment–yesterday, today, and tomorrow DOI Creative Commons

A. Y. Kim,

Salman Al Jerdi, Ryan B. MacDonald

et al.

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

Published: May 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Language: Английский

Citations

18
Protection of Alzheimer’s disease progression by a human-origin probiotics cocktail DOI Creative Commons
Santosh Kumar Prajapati, Shaohua Wang, Sidharth Mishra

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 10, 2025

Microbiome abnormalities (dysbiosis) significantly contribute to the progression of Alzheimer's disease (AD). However, therapeutic efficacy microbiome modulators in protecting against these ailments remains poorly studied. Herein, we tested a cocktail unique probiotics, including 5 Lactobacillus and Enterococcus strains isolated from infant gut with proven modulating capabilities. We aimed determine probiotics cocktail's ameliorating AD pathology humanized mouse model APP/PS1 strains. Remarkably, feeding mice 1 × 1011 CFU per day drinking water for 16 weeks reduced cognitive decline (measured by Morris Water Maze test) markers, such as Aβ aggregation, microglia activation, neuroinflammation, preserved blood-brain barrier (BBB) tight junctions. The beneficial effects were linked inflammatory microbiome, leading decreased permeability inflammation both systemic circulation brain. Although male female showed overall improvements cognition biological females did not exhibit specific markers related permeability, suggesting that underlying mechanisms may differ depending on sex. In conclusion, our results suggest this could serve prophylactic agent reduce pathology. This is achieved beneficially improving intestinal junction proteins, reducing BBB, decreasing gut, blood circulation, brain, ultimately mitigating decline.

Language: Английский

Citations

3
Taming neuroinflammation in Alzheimer's disease: The protective role of phytochemicals through the gut−brain axis DOI Open Access

Yoonsu Kim,

Jinkyu Lim, Jisun Oh

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117277 - 117277

Published: Aug. 9, 2024

Language: Английский

Citations

13
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
Kai-Xin-San ameliorates Alzheimer's disease-related neuropathology and cognitive impairment in APP/PS1 mice via the mitochondrial autophagy-NLRP3 inflammasome pathway DOI

Xiaoxiao Shan,

Wenwen Tao,

Junying Li

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 329, P. 118145 - 118145

Published: April 4, 2024

Language: Английский

Citations

11
Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease DOI Creative Commons

Eunshil Lee,

Yongmin Chang

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 168 - 168

Published: Jan. 22, 2025

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression

Language: Английский

Citations

1
Protective Effects of Bifidobacterium Breve MCC1274 as a Novel Therapy for Alzheimer’s Disease DOI Open Access
Mona Abdelhamid, Scott Counts, Chunyu Zhou

et al.

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 558 - 558

Published: Jan. 31, 2025

Alzheimer’s disease (AD) is the most common form of dementia and characterized by memory impairment that significantly interferes with daily life. Therapeutic options for AD substantively modify progression remain a critical unmet need. In this regard, gut microbiota crucial in maintaining human health regulating metabolism immune responses, increasing evidence suggests probiotics, particularly beneficial bacteria, can enhance cognitive functions. Recent studies have highlighted positive effects Bifidobacterium breve MCC1274 (B. MCC1274) on individuals mild (MCI) schizophrenia. Additionally, oral supplementation B. has been shown to effectively prevent decline AppNL–G–F mice. relation pathology, found reduce amyloid-β (Aβ) accumulation tau phosphorylation both wild-type (WT) It also decreases microglial activation increases levels synaptic proteins. review, we examine AD, exploring potential mechanisms action how probiotic strain may aid preventing or treating disease. Furthermore, discuss broader implications improving overall host provide insights into future research directions promising therapy.

Language: Английский

Citations

1
Long Non-Coding RNAs: Crucial Regulators in Alzheimer’s Disease Pathogenesis and Prospects for Precision Medicine DOI

Chenbo Yang,

Yiwei Li, Chao Chen

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

1