The Achilles heel of γ-secretase: can we contain Alzheimer's disease by reducing synthesis of β-amyloid?

Verkhratsky, Alexei; Rodrı́guez, José J.

doi:10.1038/aps.2010.189

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Astrocytes are involved in numerous physiological processes, such as neurovascular coupling, provision of nutrients to neurons, balance of extracellular ion concentration, and the uptake and release of neurotransmitters (“tripartite synapse”; Araque et al, 1999; Verkhratsky, 2010; Verkhratsky and Parpura, 2010). They also play a crucial role under pathological conditions, such as stroke, epilepsy, traumatic brain injuries, multiple sclerosis, and neurodegeneration (Verkhratsky et al, 2010; Sidoryk-Wegrzynowicz et al, 2011).…”

Section: Functional In Vivo Imagingmentioning

confidence: 99%

A Peephole into the Brain: Neuropathological Features of Alzheimer’s Disease Revealed by in vivo Two-Photon Imaging

Liebscher¹,

Meyer‐Luehmann²

2012

Front. Psychiatry

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Alzheimer’s disease (AD) is a protein conformational disorder characterized by two major neuropathological features: extracellular accumulations of amyloid-β peptides in the form of plaques and intracellular tangles, consisting of hyperphosphorylated tau proteins. Several morphological and functional changes are associated with these lesions in the diseased brain, such as dendritic and synaptic alterations, as well as microglial and astroglial recruitment and their activation. The availability of transgenic mouse models that mimic key aspects of the disease in conjunction with recent advances in two-photon imaging facilitate the study of fundamental aspects of AD pathogenesis and allow for longitudinally monitoring the efficacy of therapeutic interventions. Here, we review the ambitious efforts to understand the relationship between the main neuropathological hallmarks of AD and their associated structural and functional abnormalities by means of in vivo two-photon imaging.

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Section: Functional In Vivo Imagingmentioning

confidence: 99%

A Peephole into the Brain: Neuropathological Features of Alzheimer’s Disease Revealed by in vivo Two-Photon Imaging

Liebscher¹,

Meyer‐Luehmann²

2012

Front. Psychiatry

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“…Astrocytes are the most abundant type of glial cells in the brain and are characterized by a complex morphology with highly degree of branching. They are involved in synaptic glutamate uptake, metabolic support of the neuronal cell bodies, and processes and contracts with blood vessels (Verkhratsky and Parpura, 2010; Barzilai, 2011). Under normal physiological conditions, astroglial cells buffer extracellular K + concentrations regulate neurotrophic factors release, and control extracellular concentrations of neurotransmitters released from neighboring synapses.…”

Section: Introductionmentioning

confidence: 99%

The Role of the Neuro-Astro-Vascular Unit in the Etiology of Ataxia Telangiectasia

Meshulam¹,

Galron²,

Kanner³

et al. 2012

Front. Pharmacol.

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The growing recognition that brain pathologies do not affect neurons only but rather are, to a large extent, pathologies of glial cells as well as of the vasculature opens to new perspectives in our understanding of genetic disorders of the CNS. To validate the role of the neuron-glial-vascular unit in the etiology of genome instability disorders, we report about cell death and morphological aspects of neuroglia networks and the associated vasculature in a mouse model of Ataxia Telangiectasia (A-T), a human genetic disorder that induces severe motor impairment. We found that A-T-mutated protein deficiency was consistent with aberrant astrocytic morphology and alterations of the vasculature, often accompanied by reactive gliosis. Interestingly similar findings could also be reported in the case of other genetic disorders. These observations bolster the notion that astrocyte-specific pathologies, hampered vascularization and astrocyte-endothelium interactions in the CNS could play a crucial role in the etiology of genome instability brain disorders and could underlie neurodegeneration.

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The Achilles heel of γ-secretase: can we contain Alzheimer's disease by reducing synthesis of β-amyloid?

Cited by 2 publications

References 13 publications

A Peephole into the Brain: Neuropathological Features of Alzheimer’s Disease Revealed by in vivo Two-Photon Imaging

A Peephole into the Brain: Neuropathological Features of Alzheimer’s Disease Revealed by in vivo Two-Photon Imaging

The Role of the Neuro-Astro-Vascular Unit in the Etiology of Ataxia Telangiectasia

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