The contribution of astrocytes to Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1316-1320 ◽  
Author(s):  
Amy M. Birch
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Current Evidence ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Supporting Cells ◽  
Pathological Conditions ◽  
The Brain

Astrocytes were historically classified as supporting cells; however, it is becoming increasingly clear that they actively contribute to neuronal functioning under normal and pathological conditions. As interest in the contribution of neuroinflammation to Alzheimer's disease (AD) progression has grown, manipulating glial cells has become an attractive target for future therapies. Astrocytes have largely been under-represented in studies that assess the role of glia in these processes, despite substantial evidence of astrogliosis in AD. The actual role of astrocytes in AD remains elusive, as they seem to adopt different functions dependent on disease progression and the extent of accompanying parenchymal inflammation. Astrocytes may contribute to the clearance of amyloid β-peptide (Aβ) and restrict the spread of inflammation in the brain. Conversely, they may contribute to neurodegeneration in AD by releasing neurotoxins and neglecting crucial metabolic roles. The present review summarizes current evidence on the multi-faceted functions of astrocytes in AD, highlighting the significant scope available for future therapeutic targets.

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

scholarly journals Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Jesús Enrique García-Aviles ◽  
Rebeca Méndez-Hernández ◽  
Mara A. Guzmán-Ruiz ◽  
Miguel Cruz ◽  
Natalí N. Guerrero-Vargas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficit ◽  
Amyloid Β ◽  
Sleep Restriction ◽  
Amyloid Β Peptide ◽  
Metabolic Disturbances ◽  
The Brain ◽  
Chronic Sleep

Sleep has a major role in learning, memory consolidation, and metabolic function. Although it is known that sleep restriction increases the accumulation of amyloid β peptide (Aβ) and the risk to develop Alzheimer’s disease (AD), the mechanism behind these effects remains unknown. In this review, we discuss how chronic sleep restriction induces metabolic and cognitive impairments that could result in the development of AD in late life. Here, we integrate evidence regarding mechanisms whereby metabolic signaling becomes disturbed after short or chronic sleep restriction in the context of cognitive impairment, particularly in the accumulation of Aβ in the brain. We also discuss the role of the blood-brain barrier in sleep restriction with an emphasis on the transport of metabolic signals into the brain and Aβ clearance. This review presents the unexplored possibility that the alteration of peripheral metabolic signals induced by sleep restriction, especially insulin resistance, is responsible for cognitive deficit and, subsequently, implicated in AD development.

Recent progress on the role of GABAergic neurotransmission in the pathogenesis of Alzheimer’s disease

2016 ◽  
Vol 27 (4) ◽  
pp. 449-455 ◽  
Author(s):  
Ghulam Abbas ◽  
Wajahat Mahmood ◽  
Nurul Kabir
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gaba Receptor ◽  
Amyloid Β ◽  
Receptor Subtypes ◽  
Causative Role ◽  
Gabaergic Neurotransmission ◽  
Promising Target ◽  
The Brain

AbstractDespite their possible causative role, targeting amyloidosis, tau phosphorylation, acetylcholine esterase, glutamate, oxidative stress and mitochondrial metabolism have not yet led to the development of drugs to cure Alzheimer’s disease (AD). Recent preclinical and clinical reports exhibit a surge in interest in the role of GABAergic neurotransmission in the pathogenesis of AD. The interaction among GABAergic signaling, amyloid-β and acetylcholine is shown to affect the homeostasis between excitation (glutamate) and inhibition (GABA) in the brain. As a consequence, over-excitation leads to neurodegeneration (excitotoxicity) and impairment in the higher level functions. Previously, the glutamate arm of this balance received the most attention. Recent literature suggests that over-excitation is primarily mediated by dysfunctional GABA signaling and can possibly be restored by rectifying anomalous metabolism observed in the GABAergic neurons during AD. Additionally, neurogenesis and synaptogenesis have also been linked with GABAergic signaling. This association may provide a basis for the needed repair mechanism. Furthermore, several preclinical interventional studies revealed that targeting various GABA receptor subtypes holds potential in overcoming the memory deficits associated with AD. In conclusion, the recent scientific literature suggests that GABAergic signaling presents itself as a promising target for anti-AD drug development.

Phosphorylation of a full length amyloid-β peptide modulates its amyloid aggregation, cell binding and neurotoxic properties

2017 ◽  
Vol 13 (8) ◽  
pp. 1545-1551 ◽  
Author(s):  
Elaheh Jamasbi ◽  
Frances Separovic ◽  
Mohammed Akhter Hossain ◽  
Giuseppe Donato Ciccotosto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Full Length ◽  
Amyloid Β Peptide ◽  
Amyloid Aggregation ◽  
Cell Binding ◽  
The Brain

Phosphorylation of Aβ42 promotes the formation of amyloid plaques in the brain, which lack the neurotoxic properties associated with oligomeric species causing pathogenesis in Alzheimer's disease.

scholarly journals Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease

2020 ◽  
Author(s):  
Tasha R. Womack ◽  
Craig Vollert ◽  
Odochi Nwoko ◽  
Monika Schmitt ◽  
Sagi Montazari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Chronic Neuroinflammation ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Accumulation ◽  
Prostaglandin H ◽  
The Brain

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies, while epidemiological and experimental evidence suggests that the use of anti-inflammatory agents may be neuroprotective. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid disease pathologies. Mice overexpressing both amyloid and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of amyloid accumulation in the brain and selectively increased the production of soluble amyloid-β 42. PGI2 damaged the microvasculature through alterations in vascular length and branching; amyloid expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.

scholarly journals Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer’s disease

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Rodrigo Morales ◽  
Claudia Duran-Aniotz ◽  
Javiera Bravo-Alegria ◽  
Lisbell D. Estrada ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prion Diseases ◽  
Amyloid Β ◽  
Cerebral Amyloidosis ◽  
Amyloid Pathology ◽  
Tissue Extracts ◽  
The Brain ◽  
New Strategies

AbstractPrevious studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer’s disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aβ deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aβ aggregates accelerated amyloid pathology, supporting the concept that Aβ seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention.

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