The heterogeneity of Parkinson’s disease

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(6), P. 827 - 838

Published: May 11, 2023

The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also implicated pathophysiological pathways pose a major challenge for future research projects therapeutic trail design. We outline several concepts, mechanisms, including presumed roles α-synuclein misfolding aggregation, Lewy bodies, oxidative stress, iron melanin, deficient autophagy processes, insulin incretin signaling, T-cell autoimmunity, gut-brain axis evidence that microbial (viral) agents may induce molecular hallmarks neurodegeneration. hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) in susceptible individuals upon entry via olfactory bulb (brain first) or gut (body-first), which would support idea mechanisms change over time. unresolved have contributed to failure past trials, attempted slow course PD. thus conclude patients need personalized approaches tailored specific phenomenological etiologic subtypes disease.

Language: Английский

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Oxidative stress in Alzheimer’s disease: current knowledge of signaling pathways and therapeutics

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Jan. 2, 2024

Language: Английский

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Oxidative stress and ion channels in neurodegenerative diseases

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

Published: Jan. 29, 2024

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of channels. Abundant associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington’s disease. Reactive oxygen nitrogen species compounds trigger posttranslational alterations that target specific sites within subunits responsible for assembly. These include adjustment cysteine residues through reactions induced by reactive (ROS), nitration, S-nitrosylation assisted nitric oxide tyrosine peroxynitrite. Several channels directly investigated their functional responses to oxidizing agents stress. This review primarily explores relationship potential links between in conditions, such as cerebellar ataxias Parkinson’s correlation could hold promise developing innovative therapies common diseases.

Language: Английский

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Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e24786 - e24786

Published: Jan. 19, 2024

Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. mainly takes place owing to the imbalance anti-oxidation oxidation in body. It regulated via number factors pathways both inside outside cell. closely linked with brain various neurological disorders (NDs). In human body, contains highest levels polyunsaturated fatty acids, which are known as lipid peroxide precursors. addition, there also connection glutathione depletion peroxidation NDs. There growing evidence regarding possible link between neuroinflammation multiple NDs, such Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's Huntington's stroke. Recent studies have demonstrated that disruptions reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, other manifestations ferroptosis can be identified neuroinflammation-mediated has been reported damage-associated molecular pattern molecules including ROS generated during events cause glial activation activating neuroimmune pathways, subsequently leads generation inflammatory play role This review summarizes regulation ferroptosis, well inflammation potential range therapeutic agents used target treatment disorders.

Language: Английский

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Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions

Annals of Neurology, Journal Year: 2024, Volume and Issue: 95(4), P. 635 - 652

Published: Feb. 27, 2024

Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes multifactorial complex, evidence suggests dynamic interplay between genes the environment, emphasizing importance of identifying understanding role lifelong exposures, known as exposome, nervous system. This review provides an overview recent advances toward defining neurodegenerative disease exposomes, focusing Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease. We present current state field based emerging data, elaborate key themes potential mechanisms, conclude with limitations future directions. ANN NEUROL 2024;95:635-652.

Language: Английский

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Lactiplantibacillus (Lactobacillus) plantarum as a Complementary Treatment to Improve Symptomatology in Neurodegenerative Disease: A Systematic Review of Open Access Literature

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3010 - 3010

Published: March 5, 2024

This systematic review addresses the use of Lactiplantibacillus (Lactobacillus) plantarum in symptomatological intervention neurodegenerative disease. The existence gut microbiota dysbiosis has been associated with systemic inflammatory processes present disease, creating opportunity for new treatment strategies. involves modifying strains that constitute to enhance synaptic function through gut–brain axis. Recent studies have evaluated beneficial effects on motor and cognitive symptomatology, alone or combination. includes 20 research articles (n = 3 human n 17 animal models). main result this was combination produced improvements symptomatology related However, one included reported negative after administration plantarum. provides current relevant information about probiotic pathologies such as Alzheimer’s Parkinson’s disease Multiple Sclerosis.

Language: Английский

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3327 - 3361

Published: May 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Language: Английский

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Neuroinflammation and neurodegeneration in Huntington’s disease: genetic hallmarks, role of metals and organophosphates

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 17, 2025

Language: Английский

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Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1969 - 1969

Published: Jan. 19, 2023

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial (mtDNA). Current therapies still far from being fully effective and covering the broad spectrum of mtDNA. For example, unlike heteroplasmic conditions, MDs caused homoplasmic mtDNA do not yet benefit advances molecular approaches. An attractive method providing dysfunctional cells and/or tissues with healthy mitochondria is transplantation. In this review, we discuss what known about intercellular transfer methods used to both vitro vivo, provide an outlook on future therapeutic applications. Overall, containing wild-type copies could induce a shift even when variants present, aim attenuating preventing progression pathological clinical phenotypes. summary, transplantation challenging but potentially ground-breaking option for treatment various pathologies, although several questions remain be addressed before its application medicine.

Language: Английский

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Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer’s Disease Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10494 - 10494

Published: June 22, 2023

Liposomes modified with tetradecyltriphenylphosphonium bromide dual loading of α-tocopherol and donepezil hydrochloride were successfully designed for intranasal administration. Physicochemical characteristics cationic liposomes such as the hydrodynamic diameter, zeta potential, polydispersity index within range from 105 to 115 nm, +10 +23 mV, 0.1 0.2, respectively. In vitro release curves analyzed using Korsmeyer-Peppas, Higuchi, First-Order, Zero-Order kinetic models. Nanocontainers surfactant statistically better penetrate into mitochondria rat motoneurons. Imaging brain slices revealed penetration nanocarriers brain. Experiments on transgenic mice an Alzheimer's disease model (APP/PS1) demonstrated that administration 21 days resulted in enhanced learning abilities a reduction formation rate Aβ plaques entorhinal cortex hippocampus

Language: Английский

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