Time to test antibacterial therapy in Alzheimer’s disease

Brain, Journal Year: 2019, Volume and Issue: unknown

Published: July 25, 2019

Alzheimer's disease is associated with cerebral accumulation of amyloid-β peptide and hyperphosphorylated tau. In the past 28 years, huge efforts have been made in attempting to treat by reducing brain patients disease, no success. While anti-amyloid-β therapies continue be tested prodromal subjects at risk developing there an urgent need provide therapeutic support established for whom current symptomatic treatment (acetylcholinesterase inhibitors N-methyl d-aspartate antagonist) limited help. The possibility infectious aetiology has repeatedly postulated over three decades. Infiltration pathogens may act as a trigger or co-factor Herpes simplex virus type 1, Chlamydia pneumoniae, Porphyromonas gingivalis being most frequently implicated. These directly cross weakened blood-brain barrier, reach CNS cause neurological damage eliciting neuroinflammation. Alternatively, intestinal vascular circulation then barrier low grade chronic inflammation subsequent neuroinflammation from periphery. gut microbiota comprises complex community microorganisms. Increased permeability induced dysbiosis impact pathogenesis. Inflammatory microorganisms are peripheral deposition cognitive impairment. Oral also influence through circulatory neural access brain. At least two possibilities can envisaged explain association suspected disease. One that particularly prone microbial infections. other infection contributing Therapeutic trials antivirals and/or antibacterials could resolve this dilemma. Indeed, antiviral agents double-blind placebo-controlled studies. Although combined antibiotic therapy was found effective animal models antibacterial drugs not widely investigated This because it clear which bacterial populations overexpressed if safe, selective available them. On hand, protease inhibitor targeting P. toxins now Clinical studies needed test countering beneficial

Language: Английский

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Probiotics for Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(17), P. 4121 - 4121

Published: Aug. 23, 2019

Parkinson’s disease (PD) is a complex neurological disorder classically characterized by impairments in motor system function associated with loss of dopaminergic neurons the substantia nigra. After almost 200 years since first description PD James Parkinson, unraveling complexity continues to evolve. It now recognized that an interplay between genetic and environmental factors influences diverse range cellular processes, reflecting on other clinical features including non-motor symptoms. This has consequently highlighted extensive value early diagnosis reduce difficulties later stage management PD. Advancement understanding made remarkable progress introducing new tools strategies such as stem cell therapy deep brain stimulation. A link alterations gut microbiota also opened line. Evidence exists bidirectional pathway gastrointestinal tract central nervous system. Probiotics, prebiotics synbiotics are being examined might influence gut-brain axis altering composition, enteric system, CNS. review provides status use probiotics for Limitations future directions will be addressed promote further research considering

Language: Английский

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Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 26, 2020

Astrocytes are key homeostatic regulators in the central nervous system and play important roles physiology. After brain damage caused by e.g., status epilepticus, traumatic injury, or stroke, astrocytes may adopt a reactive phenotype. This process of astrogliosis is to restore homeostasis. However, persistent can be detrimental for contributes development epilepsy. In this review, we will focus on physiological functions normal as well pathophysiological epileptogenic brain, with acquired We discuss role astrocyte-related processes epileptogenesis, including astrogliosis, disturbances energy supply metabolism, gliotransmission, extracellular ion concentrations, blood-brain barrier dysfunction dysregulation blood flow. Since contribute epilepsy, also their potential targets new therapeutic strategies.

Language: Английский

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The Role of Gut Microbiota and Gut–Brain Interplay in Selected Diseases of the Central Nervous System

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(18), P. 10028 - 10028

Published: Sept. 17, 2021

The gut microbiome has attracted increasing attention from researchers in recent years. microbiota can have a specific and complex cross-talk with the host, particularly central nervous system (CNS), creating so-called “gut–brain axis”. Communication between gut, intestinal microbiota, brain involves secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components bacteria, signaling molecules. Moreover, an imbalance composition modulates immune function tissue barriers blood–brain barrier (BBB). Therefore, aim this literature review is to describe how gut–brain interplay may contribute development neurological disorders, combining fields gastroenterology neuroscience. We present findings concerning effect altered on neurodegeneration neuroinflammation, including Alzheimer’s Parkinson’s diseases, well multiple sclerosis. impact pathological shift selected neuropsychological i.e., major depressive disorders (MDD) autism spectrum disorder (ASD), also discussed. Future research balanced axis would help identify new potential opportunities for therapeutic interventions presented diseases.

Language: Английский

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Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

Frontiers in Cellular and Infection Microbiology, Journal Year: 2019, Volume and Issue: 9

Published: May 28, 2019

Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur only a fraction of individuals with genetic predisposition and conversely, no risk disorder develop one. Chronic like Alzheimer's, Parkinson's, multiple sclerosis are speculated to result from combination environmental factors, concept commonly referred as the "multiple hit hypothesis". A number bacterial infections have been linked increased neurodegeneration, some cases, clearance pathogens has correlated amelioration CNS deficits. Additionally, mutations several genes known contribute disorders Parkinson's Disease repeatedly implicated susceptibility intracellular infection. Recent data begun demonstrate roles for these (Parkin, PINK1, LRRK2) modulating innate immune outcomes, suggesting that dysregulation may play an even more important role neurodegeneration than previously appreciated. This review will broadly explore connections between infection, dysregulation, central nervous system (CNS) disorders. Understanding this interplay how pathogenesis contributes "multiple-hit hypothesis" be crucial therapeutics effectively treat both

Language: Английский

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