Antiviral agents in Alzheimer’s disease: hope for the future?

Wozniak, Matthew A.; Itzhaki, Ruth F.

doi:10.1177/1756285610370069

Cited by 44 publications

(40 citation statements)

References 75 publications

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“…Other viri including influenza PR8 virus may gain entry via nasal and/or oral portals, promote CNS neuroinflammation, and cause widespread neuronal dysfunction, including those of the NTS. Similar to HSV1, hepatitis, HIV, West Nile virus, Chlamydia pneumoniae and Borrelia burgdorferi (to name just a few), are capable of causing CNS pathology [299], as are other bacteria [70]. Injection of pseudorabies virus in the rat genioglossus produced viral labeling in neurons of the hypoglossal and the NTS nuclei [300].…”

Section: Invading Pathogens Cause Nts Dysfunctionmentioning

confidence: 98%

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

Daulatzai

2012

Neurochem Res

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The pathophysiological mechanism(s) underlying Alzheimer's disease (AD) still remain unclear, and no disease-modifying or prophylactic therapies are currently available. Unraveling the fundamental neuropathogenesis of AD is an important challenge. Several studies on AD have suggested lesions in a number of CNS areas including the basal forebrain, hippocampus, entorhinal cortex, amygdale/insula, and the locus coeruleus. However, plausible unifying studies on the upstream factors that involve these heterogeneous regions and herald the onset of AD pathogenesis are not available. The current article presents a novel nucleus tractus solitarius (NTS) vector hypothesis that underpins several disparate biological mechanisms and neural circuits, and identifies relevant hallmarks of major presumptive causative factor(s) linked to the NTS, in older/aging individuals. Aging, obesity, infection, sleep apnea, smoking, neuropsychological states, and hypothermia-all activate inflammatory cytokines and oxidative stress. The synergistic impact of systemic proinflammatory mediators activates microglia and promotes neuroinflammation. Acutely, the innate immune response is protective defending against pathogens/toxins; however, when chronic, it causes neuroinflammation and neuronal dysfunction, particularly in brainstem and neocortex. The NTS in the brainstem is an essential multiple signaling hub, and an extremely important central integration site of baroreceptor, chemoreceptor, and a multitude of sensory afferents from gustatory, gastrointestinal, cardiac, pulmonary, and upper airway systems. Owing to persistent neuroinflammation, the dysfunctional NTS exerts deleterious impact on nucleus ambiguus, dorsal motor nucleus of vagus, hypoglossal, parabrachial, locus coeruleus and many key nuclei in the brainstem, and the hippocampus, entorhinal cortex, prefrontal cortex, amygdala, insula, and basal forebrain in the neocortex. The neuronal and synaptic dysfunction emanating from the inflamed NTS may affect its interconnected pathways impacting almost the entire CNS--which is already primed by neuroinflammation, thus promoting cognitive and neuropsychiatric symptoms. The upstream factors discussed here may underpin the neuropathopgenesis of AD. AD pathology is multifactorial; the current perspective underscores the value of attenuating disparate upstream factors--in conjunction with anticholinesterase, anti-inflammatory, immunosuppressive, and anti-oxidant pharmacotherapy. Amelioration of the NTS pathology may be of central importance in countering the neuropathological cascade of AD. The NTS, therefore, may be a potential target of novel therapeutic strategies.

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Section: Invading Pathogens Cause Nts Dysfunctionmentioning

confidence: 98%

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

Daulatzai

2012

Neurochem Res

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“…The association between Helicobacter pylori ( H. pylori ) infection and AD has recently been addressed [3], and other infections [i.e., Chlamydia pneumoniae ( C. pneumoniae ), cytomegalovirus, and herpes simplex virus type1] may influence AD manifestation [4]. Furthermore, inflammation-mediated damage in the apolipoprotein E (ApoE) allele 4 suggests a plausible marker for cognitive impairment, possibly due to increased viral replication, which could eventually lead to AD [5]. One way to affect this relationship is by controlling risk factors (e.g., diabetes, cholesterol, hypertension, stroke, or smoking) that could help alleviate physiological dementia risk factors [6].…”

Section: Introductionmentioning

confidence: 99%

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study

et al. 2016

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BackgroundRecent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD.MethodsA total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD.ResultsAmong CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710–13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010–0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein).ConclusionsThe current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.

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“…Acyclovir, penciclovir, and foscarnet were found to reduce Aβ and p-tau levels in AD cell models (table 1) [41]. …”

Section: Resultsmentioning

confidence: 99%

A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents

Appleby¹,

Nacopoulos²,

Milano³

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: Many compounds that have already been approved for alternate diagnoses have been studied in relation to Alzheimer’s disease (AD). The purpose of this review is to summarize these studies and discuss the rationale and benefits of repurposing drugs for AD treatment. Methods: Studies of drugs related to AD treatment that were relevant to a disease-modifying mechanism of action (MOA) and are already approved by the Food and Drug Administration for non-AD diagnoses were collected from PubMed. Results: Many drugs already approved for the treatment of other diseases have been studied in relation to AD treatment. Numerous drugs with known toxicity profiles have the potential to be repurposed as a treatment for AD. Conclusion: Known MOA, toxicology, and pharmacodynamic profiles would accelerate the process and increase the odds of finding a more timely disease-modifying treatment for AD.

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Antiviral agents in Alzheimer’s disease: hope for the future?

Cited by 44 publications

References 75 publications

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study

A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents

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