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

Brain metabolism in Alzheimer’s disease: biological mechanisms of exercise DOI Creative Commons

Longfei Xu,

Ran Liu,

Yingkai Qin

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: June 26, 2023

Alzheimer's disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation multiple adverse factors, accompanied dysregulation numerous intracellular signaling molecular pathways in the brain. At cellular levels, neuronal milieu AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, reduced overall capacity, which lead to abnormal neural network activity neuroplasticity, thus accelerating formation extracellular senile plaques neurofibrillary tangles. The current absence effective pharmacological therapies for points urgent need investigate benefits non-pharmacological approaches such as physical exercise. Despite evidence that regular can improve dysfunction state, inhibit different pathophysiological associated with AD, influence pathological process exert protective effect, there no clear consensus on specific biological mechanisms underlying advantages Here, we review how exercise improves crucial processes disorders including glucose Aβ metabolism transport, iron tau pathology. How states health also presented. A better knowledge neurophysiological contribute development novel drugs improvement interventions.

Language: Английский

Citations

39
Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice DOI Creative Commons
Xiaohang Qian, Wangxi Hai, Siyue Chen

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Nov. 22, 2023

Numerous studies have described the notable impact of gut microbiota on brain in Alzheimer's disease (AD) via – axis. However, molecular mechanisms underlying involvement development AD are limited. This study aimed to explore potential by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months age were used as mouse model. Cognitive function was assessed using Morris water maze test. The levels Aβ plaque neuroinflammation detected immunofluorescence PET/CT. addition, we not only 16S rRNA gene sequencing metabolomics variation characteristics serum metabolism abundance, but also combined spatial transcriptomics change identify their correlation. showed significant cognitive impairment amyloid-β deposits brain. abundance significantly changed mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, Ruminococcus increased Pseudomonas. integration untargeted that glycerophospholipid a common alteration pathway mice. Significant proliferation activation astrocyte microglia observed accompanied alterations immune pathways. Integration analysis fecal transplantation (FMT) intervention revealed association microbiota, host metabolism,

Language: Английский

Citations

37
Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects DOI

Pushank Nagar,

Prajjwal Sharma,

Rishika Dhapola

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 330, P. 121983 - 121983

Published: July 29, 2023

Language: Английский

Citations

32
Targeting protein kinases for the treatment of Alzheimer's disease: Recent progress and future perspectives DOI
Zhijia Li, Bo Yin,

Shuangqian Zhang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 261, P. 115817 - 115817

Published: Sept. 14, 2023

Language: Английский

Citations

31
PPAR agonists for the treatment of neuroinflammatory diseases DOI

Celene Titus,

Md. Tozammel Hoque, Reina Bendayan

et al.

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 45(1), P. 9 - 23

Published: Dec. 7, 2023

Language: Английский

Citations

31
Alzheimer’s disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy? DOI Creative Commons

Daniela Melchiorri,

Sara Merlo, Benjamin Micallef

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: June 2, 2023

Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer’s disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading dementia and death, characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal neurofibrillary tangles (NFTs) consisting altered hyperphosphorylated tau protein. Both have been widely studied pharmacologically targeted for many years, without significant results. In 2022, positive data on monoclonal antibodies targeting Aβ, donanemab lecanemab, followed 2023 FDA accelerated approval lecanemab publication final results phase III Clarity AD study, strengthened hypothesis causal role Aβ in pathogenesis AD. However, magnitude clinical effect elicited drugs limited, suggesting that additional mechanisms may contribute disease. Cumulative studies shown inflammation as one main contributors recognition specific neuroinflammation synergic with NFTs cascades. The present review provides an overview investigational are trials. Moreover, their action, positioning cascade events occur brain throughout potential benefit/limitation strategy discussed highlighted well. addition, latest patent requests inflammation-targeting therapeutics be developed will also discussed.

Language: Английский

Citations

26
The role of high mobility group box 1 in neuroinflammatory related diseases DOI Open Access

Jialu Mo,

Jiao Hu,

Xianglin Cheng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114541 - 114541

Published: March 22, 2023

High mobility group box 1 (HMGB1) is a ubiquitous and highly conserved non-histone DNA-binding protein with different biological functions according to its subcellular localization. It widely believed that HMGB1, which released into the extracellular space, plays key role in inflammatory response. In recent years, numerous studies have shown development of various neurological diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), multiple (MS), cerebrovascular traumatic brain injury (TBI) are inextricably linked inflammation. We will review mechanisms HMGB1 receptors nervous system inflammation provide basis for further new HMGB1-based therapies.

Language: Английский

Citations

23
The neurotransmitter puzzle of Alzheimer's: Dissecting mechanisms and exploring therapeutic horizons DOI
Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1829, P. 148797 - 148797

Published: Feb. 10, 2024

Language: Английский

Citations

15
Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health DOI
Sebastián García Menéndez, Walter Manucha

Current Pharmaceutical Design, Journal Year: 2024, Volume and Issue: 30(5), P. 323 - 332

Published: Feb. 1, 2024

Abstract: Neuroinflammation represents a critical immune response within the brain, playing pivotal role in defense against injury and infection. However, when this becomes chronic, it can contribute to development of various neurodegenerative psychiatric disorders. This bibliographic review delves into vitamin D modulating neuroinflammation its implications for brain health, particularly context neurological While is traditionally associated with calcium homeostasis bone also exerts immunomodulatory neuroprotective effects central nervous system. Through comprehensive analysis preclinical clinical studies, we uncover how D, acting through receptors glial cells, may influence production proinflammatory cytokines antioxidants, potentially mitigating cascade events leading neuronal damage. Clinical research has identified deficiency as common thread increased risks multiple sclerosis, Parkinson's disease, Alzheimer's, depression, among others. Furthermore, models suggest D's regulatory capacity over inflammatory mediators, protective apoptosis, contribution neurogenesis synaptic plasticity. These insights underscore potential supplementation not only slowing progression diseases but improving quality life patients suffering from conditions. Future studies are essential validate these findings further our understanding prevent or alleviate symptoms, opening new avenues therapeutic strategies neuroinflammation-related pathologies. crucial injuries infections, persistence lead such Parkinson's, depression. Cholecalciferol (Vitamin D3) emerges regulator neuroinflammation, present cells astrocytes microglia, function. Vitamin mechanisms action include cytokine modulation regulation nuclear mitochondrial genes. It adjusts mediators resulting effects. Additionally, impacts neurotransmitter synthesis positions adjunct treating like Alzheimer's Parkinson's. Lastly, intestinal microbiota serotonin contributes disorders schizophrenia Thus, presents novel approach neuroinflammatory, neurodegenerative, neuropsychiatric diseases.

Language: Английский

Citations

13
The role of CD56bright NK cells in neurodegenerative disorders DOI Creative Commons
Carla Rodriguez-Mogeda,

Chaja M. J. van Ansenwoude,

Lennart van der Molen

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 13, 2024

Abstract Emerging evidence suggests a potential role for natural killer (NK) cells in neurodegenerative diseases, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. However, the precise function of NK these diseases remains ambiguous. The existence two cell subsets, CD56 bright dim cells, complicates understanding contribution neurodegeneration their functions within context may differ significantly. are potent cytokine secretors considered more immunoregulatory less terminally differentiated than mostly cytotoxic counterparts. Hence, this review focusses on specifically diseases. Moreover, it explores mechanisms underlying ability to enter central nervous system. By consolidating current knowledge, we aim provide comprehensive overview Elucidating impact have implications future therapeutic interventions, potentially ameliorating pathogenesis.

Language: Английский

Citations

13