Neurodegenerative Disease and the NLRP3 Inflammasome

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Март 10, 2021

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by progressive neuronal loss the brain or peripheral nervous system, generally involve protein aggregation, as well metabolic abnormalities immune dysregulation. Although vast majority neurodegeneration idiopathic, there many known genetic environmental triggers. In past decade, research exploring low-grade systemic inflammation its impact on development progression increased. A particular focus been whether arises only secondary effect also cause pathology. inflammasomes, more specifically NLRP3 inflammasome, crucial component innate usually activated response infection tissue damage. Dysregulation inflammasome implicated several disorders, such Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis, prion diseases. This review aims summarise current literature role pathogenesis diseases, work investigating inhibition potential future therapy.

Язык: Английский

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Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Cells, Год журнала: 2022, Номер 11(16), С. 2607 - 2607

Опубликована: Авг. 21, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently, growing preclinical studies have that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among others. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Язык: Английский

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Biological Effects of Indole-3-Propionic Acid, a Gut Microbiota-Derived Metabolite, and Its Precursor Tryptophan in Mammals’ Health and Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1222 - 1222

Опубликована: Янв. 22, 2022

Actions of symbiotic gut microbiota are in dynamic balance with the host’s organism to maintain homeostasis. Many different factors have an impact on this relationship, including bacterial metabolites. Several substrates for their synthesis been established, tryptophan, exogenous amino acid. biological processes influenced by action tryptophan and its endogenous metabolites, serotonin, melatonin. Recent research findings also provide evidence that bacteria-derived metabolites share effects precursor. Thus, review aims investigate actions indole-3-propionic acid (IPA), a microbiota-derived metabolite tryptophan. We searched PUBMED Google Scholar databases identify pre-clinical clinical studies evaluating IPA health pathophysiology immune, nervous, gastrointestinal cardiovascular system mammals. exhibits similar energetic precursor, Additionally, has positive cellular level, preventing oxidative stress injury, lipoperoxidation inhibiting proinflammatory cytokines. Its can be diminished presence risk atherosclerosis. On other hand, protective factors, such as introduction Mediterranean diet, tend increase plasma concentration. seems promising new target, linking system.

Язык: Английский

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Apoptosis and its therapeutic implications in neurodegenerative diseases

Clinical Anatomy, Год журнала: 2021, Номер 35(1), С. 65 - 78

Опубликована: Сен. 24, 2021

Neurodegenerative disorders are characterized by progressive loss of particular populations neurons. Apoptosis has been implicated in the pathogenesis neurodegenerative diseases, including Parkinson disease, Alzheimer Huntington and amyotrophic lateral sclerosis. In this review, we focus on existing notions relevant to comprehending apoptotic death process, morphological features, mediators regulators cellular apoptosis. We also highlight evidence neuronal Additionally, present potential therapeutic agents that could modify pathway aforementioned diseases delay disease progression. Finally, review clinical trials were conducted evaluate use anti-apoptotic drugs treatment order essential need for early detection intervention humans.

Язык: Английский

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Neuroprotective Potential of Limonene and Limonene Containing Natural Products

Molecules, Год журнала: 2021, Номер 26(15), С. 4535 - 4535

Опубликована: Июль 27, 2021

Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there notable interest in investigating pharmacological effects limonene various chronic diseases due its mitigating effect on oxidative stress inflammation regulating apoptotic cell death. There are available studies demonstrating neuroprotective role neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, stroke. The high abundance nature, safety profile, mechanisms action make this favorable molecule be developed nutraceutical for preventive purposes an alternative agent or adjuvant modern therapeutic drugs curbing onset progression diseases. This manuscript presents comprehensive review scientific literature discussing activities plant products containing which attribute protective ability disorders. has been compiled based existing published articles limonene-containing natural investigated their neurotherapeutic potential. All English abstract were extracted from different databases that offer access diverse journals. These PubMed, Scopus, Google Scholar, Science Direct. Collectively, emphasizes potential against other neuroinflammatory data indicative nutritional use actions may direct future preclinical clinical development complementary phytomedicine. pharmacophore can also provide blueprint further drug discovery using numerous tools.

Язык: Английский

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