scholarly journals Alzheimer´s Disease in the Perspective of Neuroimmunology

2018 ◽  
Vol 12 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Ricardo B. Maccioni ◽  
Andrea González ◽  
Víctor Andrade ◽  
Nicole Cortés ◽  
José Pablo Tapia ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Tau Protein ◽  
Microglial Activation ◽  
Neurodegenerative Disorder ◽  
Vicious Cycle ◽  
Considerable Research ◽  
Dopaminergic Pathway ◽  
The World ◽  
Main Culprit

Background:Alzheimer’s Disease (AD) is a severe neurodegenerative disorder that includes the occurrence of behavioral disorders as well as memory and cognitive impairment as major symptoms. AD affects around 12% of the aged population in the world. Considerable research efforts have pointed to the role of innate immunity as the main culprit in the pathogenesis of AD. In this context, and according to with our neuroimmunomodulation theory, microglial activation modifies the cross-talks between microglia and neurons. We postulated that glial activation triggered by “damage signals” activates a pathological molecular cascade that finally leads to hyperphosphorylation and oligomerization of the tau protein. Interestingly, these modifications correlate with the gradual cognitive impairment of patients with the AD. Microglial activation is determined by the nature and strength of the stimulus. In the AD, a continuous activation state of microglia appears to generate neuronal injury and neurodegeneration, producing the outflow of pathological tau from the inner of neurons to the extraneuronal space. Released tau, together with the contribution of ApoE4 protein, would then produce reactivation of microglia, thus inducing a positive feedback that stimulates the vicious cycle in neurodegeneration.Conclusion:Nevertheless, from the pathophysiological perspective AD is significantly more than a loss of memory. In the initial stages of AD pathogenesis, variations in the dopaminergic pathway along with serotonin diminution play an important role. This may explain why depression is associated with the onset of AD. All these pathophysiological events take place together with immunomodulatory changes that trigger tau oligomerization in the course of neurofibrillary tangles formation. Interestingly, mood disorders appear to be followed by neuroinflammatory processes and structural/functional alterations that lead to cognitive impairment in the context of AD.

The role of tau-protein in the diagnosis of cognitive impairment in diabetes

2020 ◽  
Author(s):  
Mariia Matveeva ◽  
Julia Samoilova ◽  
Natalie Zhukova
Keyword(s):  
Cognitive Impairment ◽  
Tau Protein

scholarly journals Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

2018 ◽  
Vol 107 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Maud Gratuze ◽  
Aurélie Joly-Amado ◽  
Didier Vieau ◽  
Luc Buée ◽  
David Blum
Keyword(s):  
Tau Protein ◽  
Energy Homeostasis ◽  
Neurodegenerative Disorder ◽  
Insulin Signalling ◽  
Positive Outcome ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Multiple Levels ◽  
The Brain

Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

scholarly journals New Therapeutic Approaches to Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo Biloba (EGb 761®)

2021 ◽  
Author(s):  
Carlo Tomino ◽  
Sara Ilari ◽  
Vincenzo Solfrizzi ◽  
Valentina Malafoglia ◽  
Guglielmo Zilio ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Combination Therapy ◽  
Cognitive Decline ◽  
Ginkgo Biloba ◽  
Neurodegenerative Disorder ◽  
Mild Dementia ◽  
Dementia Syndrome

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

scholarly journals Cognitive impairment in patients with atrial fibrillation

2020 ◽  
Vol 4 (9) ◽  
pp. 578-583
Author(s):  
E.V. Mityaeva ◽  
◽  
P.R. Kamchatnov ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Tau Protein ◽  
Small Vessel Disease ◽  
Cardioembolic Stroke ◽  
Small Vessel ◽  
Vessel Disease ◽  
Increased Risk

Atrial fibrillation (AF) is an important medical and social problem due to its wide prevalence in the population and high risk of embolic complications leading to severe consequences. The article describes an association established between AF and an increased risk of cognitive impairment (CI). Cardioembolic stroke due to AF is a common cause of CI, however, there are other mechanisms for CI development. The article also examines the role of small vessel disease and asymptomatic cerebral infarction in the formation of CI in patients with AF. Adding that, it provides data on the AF role in the development of neurodegenerative process with the accumulation of amyloid and tau protein in the brain tissue. There is an increased risk of Alzheimer’s disease in patients with AF, although the causal relationship of these conditions requires clarification. Modern data concerning the role of neuroinflammation and genetic predisposition in the development of CI in AF were analyzed. The conclusion is made about the pathogenetic heterogeneity of higher cerebral functions disorders on the basis of the presented data on the CI pathogenetic mechanism in patients with AF and comorbid conditions. It was suggested that the optimal pathogenetic therapy can be chosen taking into account the known CI pathogenetic mechanisms. KEYWORDS: atrial fibrillation, cognitive impairment, dementia, Alzheimer’s disease, cardioembolic stroke, small vessel disease, neurodegeneration, amyloid, tau protein, pathogenesis. FOR CITATION: Mityaeva E.V., Kamchatnov P.R. Cognitive impairment in patients with atrial fibrillation. Russian Medical Inquiry. 2020;4(9):578–583. DOI: 10.32364/2587-6821-2020-4-9-578-583.

Role of natural plant products against Alzheimer’s disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Himanshi Varshney ◽  
Yasir Hasan Siddique
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Cholinesterase Inhibitors ◽  
Amyloid Fibrils ◽  
Therapeutic Agent ◽  
Neurodegenerative Disorder ◽  
Natural Plant ◽  
Plant Products

: Alzheimer’s disease (AD) is one of the major neurodegenerative disorder. Deposition of amyloid fibrils and tau protein are associated with various pathological symptoms. Currently limited medication is available for AD treatment. Most of the drugs are basically cholinesterase inhibitors and associated with various side effects. Natural plant products have shown potential as a therapeutic agent for the treatment of AD symptoms. Variety of secondary metabolites like flavonoids, tannins, terpenoids, alkaloids and phenols are used to reduce the progression of the disease. Plant products have less or no side effect and are easily available. The present review gives a detailed account of the potential of natural plant products against the AD symptoms.

scholarly journals Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract Tumours

2009 ◽  
Vol 60 (4) ◽  
pp. 465-483 ◽  
Author(s):  
Annie Pfohl-Leszkowicz
Keyword(s):  
Ochratoxin A ◽  
Aristolochic Acid ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Balkan Endemic Nephropathy ◽  
Aristolochic Acids ◽  
The World ◽  
Main Culprit ◽  
Endemic Nephropathy

Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract TumoursThis review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA- and AA-DNA adduct formation; the role of genetic polymorphisms; and the risk for young children.

scholarly journals Impaired Signaling of NF-κB and NRF2 in CX3CR1-Deficient Microglia: Implications in Tauopathies

2018 ◽  
Author(s):  
Sara Castro-Sánchez ◽  
Ángel J. García-Yagüe ◽  
Sebastian Kügler ◽  
Isabel Lastres-Becker
Keyword(s):  
Transcription Factor ◽  
Tau Protein ◽  
Microglial Activation ◽  
Potential Role ◽  
Early Response ◽  
Therapeutic Strategies ◽  
Low Grade

ABSTRACTTAU protein aggregation is the main characteristic of neurodegenerative diseases known as tauopathies. Low-grade chronic inflammation is also another hallmark that indicates crosstalk between damaged neurons and glial cells. We have demonstrated that neurons overexpressing TAUP301L release CX3CL1, which activates anti-inflammatory NRF2 signalling in microglial cells in vitro and in vivo. However, the potential role of CX3CR1 in the context of tauopathies and its implication in neuroinflammation are poorly described. In this work we show that CX3CL1 activates the pro-inflammatory pathway as an early response mediated by the transcription factor NF-κB through the activation of mitogen-and stress-activated protein kinase-1 (MSK-1). At a functional level, CX3CR1-deficient microglia show decreased expression of NRF2, impaired cell migration and deficiency of phagocytosis. The relevance of these findings is evident in a tauopathy model, where the treatment with an inducer of NRF2, sulforaphane, is able to modulate astrogliosis but not microgliosis. These findings suggest that CX3CR1/NRF2 axis is essential in microglial activation associated with tauopathies and that polymorphisms have to be taken into account to development of therapeutic strategies

scholarly journals Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches

2021 ◽  
Vol 11 (11) ◽  
pp. 1116
Author(s):  
Shadab Md ◽  
Nabil A. Alhakamy ◽  
Mohamed A. Alfaleh ◽  
Obaid Afzal ◽  
Abdulmalik S. A. Altamimi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Microglial Activation ◽  
Neurodegenerative Disorder ◽  
Limiting Factor ◽  
Therapeutic Approaches ◽  
Hyperphosphorylated Tau Protein ◽  
Gsk 3Β ◽  
Ad Therapy

Alzheimer’s disease (AD) is a common neurodegenerative disorder accountable for dementia and cognitive dysfunction. The etiology of AD is complex and multifactorial in origin. The formation and deposition of amyloid-beta (Aβ), hyperphosphorylated tau protein, neuroinflammation, persistent oxidative stress, and alteration in signaling pathways have been extensively explored among the various etiological hallmarks. However, more recently, the immunogenic regulation of AD has been identified, and macroglial activation is considered a limiting factor in its etiological cascade. Macroglial activation causes neuroinflammation via modulation of the NLRP3/NF-kB/p38 MAPKs pathway and is also involved in tau pathology via modulation of the GSK-3β/p38 MAPK pathways. Additionally, microglial activation contributes to the discrete release of neurotransmitters and an altered neuronal synaptic plasticity. Therefore, activated microglial cells appear to be an emerging target for managing and treating AD. This review article discussed the pathology of microglial activation in AD and the role of various nanocarrier-based anti-Alzeihmenr’s therapeutic approaches that can either reverse or inhibit this activation. Thus, as a targeted drug delivery system, nanocarrier approaches could emerge as a novel means to overcome existing AD therapy limitations.

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