Role of Microbes in the Development of Alzheimer’s Disease: State of the Art – An International Symposium Presented at the 2017 IAGG Congress in San Francisco

Frontiers in Genetics, Journal Year: 2018, Volume and Issue: 9

Published: Sept. 10, 2018

This article reviews research results and ideas presented at a special symposium the International Association of Gerontology Geriatrics (IAGG) Congress held in July 2017 San Francisco. Five researchers their related to infection Alzheimer's disease (AD). Prof. Itzhaki her work on role viruses, specifically HSV-1, pathogenesis AD. She maintains that although it is true most people harbor HSV-1 infection, either latent or active, nonetheless aspects herpes can play AD, based extensive experimental evidence from AD brains infected cell cultures. Dr. Miklossy high prevalence bacterial infections correlate with spirochete infections, which have been known for decades be significant cause dementia (e.g., syphilis). demonstrated how spirochetes drive senile plaque formation, are fact biofilms. Balin then described involvement brain tissue by Chlamydia pneumoniae bacterium, its potential use innate immune system spread, initiation damage characteristic Fülöp AD-associated amyloid beta (A) peptide as an antibacterial, antifungal antiviral effector produced reaction microorganisms attack brain. Barron put forward novel hypothesis that, according experiments, there strong sequence-specific binding between A another ubiquitous important human effector, cathelicidin LL-37. Given this binding, LL-37 expression will decrease deposition via formation non-toxic, soluble A/LL-37 complexes. Therefore, chronic under-expression could factor simultaneously permits allows pathological accumulation A. first-of-its-kind opened way paradigm shift studying "amyloid cascade hypothesis", so far has quite unsuccessful, new "infection perhaps more broadly, "innate dysregulation may well permit lead discovery treatments patients.

Language: Английский

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Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection

Molecular Neurobiology, Journal Year: 2020, Volume and Issue: 58(2), P. 520 - 535

Published: Sept. 25, 2020

The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on immediate risks and impact system; however, effects induced to central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 can dramatically affect brain function exacerbate neurodegenerative diseases in patients, but mechanisms not been entirely described. In this review, we gather information from past actual studies coronaviruses informed neurological dysfunction damage. Then, analyzed described possible causative injury after infection. We proposed potential routes neuro-invasion determinant factors process. considered hematogenous route directly microvascular endothelium cells integrate blood-brain barrier be fundamental initiation Additionally, activation inflammatory response against represents a critical step induction tissue. Consequently, virus' ability infect induce promote or increase risk acquire diseases. Here, contribute understanding conditions found patients with its association integrity.

Language: Английский

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Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

Frontiers in Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: Dec. 12, 2017

Mast cells are localized throughout the body and mediate allergic, immune inflammatory reactions. They heterogeneous, tissue-resident, long-lived granulated cells. increase their numbers in specific site by proliferation, increased recruitment, survival rate of maturation from its progenitors. implicated brain injuries, neuropsychiatric disorders, stress, neuroinflammation neurodegeneration. Brain mast first responders before microglia injuries since can release prestored mediators. also detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate to newly synthesized mediators induce blood-brain barrier permeability, recruitment into neuroinflammation. induces corticotropin-releasing hormone (CRH) paraventricular nucleus hypothalamus CRH activates glial through receptors releases neuroinflammatory increases proinflammatory mediator peripheral systems that augment Post-traumatic stress disorder (PTSD) is a traumatic-chronic related mental dysfunction. Currently there no therapy treat PTSD mechanisms not yet clearly understood. Moreover, recent reports indicate could neurodegeneration pathogenesis neurodegenerative diseases. play crucial role inflammation as well due depression PTSD. Therefore, activation injury, may accelerate diseases including AD. This review focusses on how promote We suggest inhibition associated pathways be explored new therapeutic target delay or prevent severity

Language: Английский

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Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer’s Rat Model

Medicine & Science in Sports & Exercise, Journal Year: 2017, Volume and Issue: 50(5), P. 945 - 956

Published: Dec. 12, 2017

This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease (AD) rat model and provide an initial understanding related molecular mechanisms.Male 2.5-month-old Sprague-Dawley rats were divided into following four groups: (a) control, (b) swim + vehicle, (c) STZ without swim, (d) STZ. The Barnes maze task novel object recognition test used measure hippocampus-dependent spatial learning working memory, respectively. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) kits assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, enzymes, amyloid-beta production, tau hyperphosphorylation.Behavioral tests revealed that could significantly inhibit STZ-induced cognitive dysfunction (P < 0.05). animals displayed significant loss presynaptic/postsynaptic markers in hippocampal CA1 was reversed by also increased reactive gliosis, release proinflammatory oxidative damage, attenuated preexercise 0.05, between-treatment changes). Likewise, induced protein expression 0.001) DNA-binding activity = 0.015) Nrf2 downstream gene region had levels (1-42) hyperphosphorylation ameliorated Histological studies showed imparted substantial neuroprotection 0.001), suppressing neuronal apoptosis-like cell death compared with control group 0.001).Exercise pretraining exerts multifactorial benefits AD support its use as promising new therapeutic option for prevention neurodegeneration elderly and/or population.

Language: Английский

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Lipopolysaccharide (LPS) Accumulates in Neocortical Neurons of Alzheimer’s Disease (AD) Brain and Impairs Transcription in Human Neuronal-Glial Primary Co-cultures

Frontiers in Aging Neuroscience, Journal Year: 2017, Volume and Issue: 9

Published: Dec. 11, 2017

Several independent laboratories have recently reported the detection of bacterial nucleic acid sequences or bacterial-derived neurotoxins, such as highly inflammatory lipopolysaccharide (LPS), within Alzheimer's disease (AD) affected brain tissues. Whether these neurotoxins originate from gastrointestinal (GI) tract microbiome, a possible microbiome some dormant pathological is currently not well understood. Previous studies indicating that co-localization pro-inflammatory LPS with AD-affected cell nuclei suggests there may be contribution this neurotoxin to genotoxic events support neurodegeneration and failure in homeostatic gene expression. In report we provide evidence sporadic AD, progressively accumulates neuronal parenchyma appears preferentially associate periphery nuclei. Run-on transcription utilizing [α-32P]-uridine triphosphate incorporation into newly synthesized total RNA further indicates human neuronal-glial (HNG) cells primary co-culture incubated exhibit significantly reduced output DNA products. These suggest AD impair efficient readout genetic information normally required for operation function contribute progressive disruption read-out information.

Language: Английский

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