Modulation of mitochondrial calcium as a pharmacological target for Alzheimer's disease

Hung, Clara Hiu Ling; Ho, Yuen Shan; Chang, Raymond Chuen‐Chung

doi:10.1016/j.arr.2010.05.003

Cited by 41 publications

(30 citation statements)

References 115 publications

(131 reference statements)

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“…Ab is also associated with modulation of mitochondrial Ca 2? levels leading to alterations in organelle physiology and enhancing self fragmentation [105]. Being metabolically highly active, aberrant mitochondrial function in photoreceptors and RPE can have a significant impact in AMD.…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

Gupta

Chitranshi

et al. 2016

Cell. Mol. Life Sci.

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Accumulation of amyloid β (Aβ) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of Aβ accumulation as well as its in vivo roles remains elusive; nonetheless, the majority of the efforts to address pathological mechanisms for therapeutic development are focused towards moderating Aβ accumulation in the brain. More recently, Aβ deposition has been identified in the eye and is linked with distinct age-related diseases including age-related macular degeneration, glaucoma as well as AD. Awareness of the Aβ accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for Aβ and the potential to use retina as a model for brain related neurodegenerative disorders. Here, we present an integrated view of current understanding of the retinal Aβ deposition discussing the accumulation mechanisms, anticipated impacts and outlining ameliorative approaches that can be extrapolated to the retina for potential therapeutic benefits. Further longitudinal investigations in humans and animal models will determine retinal Aβ association as a potential pathognomonic, diagnostic or prognostic biomarker.

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Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

Gupta

Chitranshi

et al. 2016

Cell. Mol. Life Sci.

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“…Impairment of fission and fusion has been considered to be one of the pathophysiological indexes in AD (Santos et al 2010). There are some suggestions that Aβ peptides will modulate the cytosolic Ca 2+ level in mitochondria that may alter the mitochondrial morphology and physiology (Hung et al 2010). For example, elevated cytosolic Ca 2+ level may enhance the fragmentation of mitochondria and hence lead to the perturbation of fission and fusion balance which may eventually cause mitochondrial dysfunction (Saotome et al 2008).…”

Section: Ad-related Retinal Degeneration Advancing Both the Retinal Dmentioning

confidence: 99%

Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina?

Chiu

Chan

et al. 2011

AGE

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Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models.

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“…Three-dimensional structure analysis revealed that Aβ oligomers could form a channel in bilayer, and another study showed the channel display a strong selective affinity for Calcium (Figure 2) [115,116]. Therefore, the “modulation of mitochondrial calcium as a pharmacological target for Alzheimer’s disease” has been recently proposed [117]. …”

Section: The Potential Of the Mcu As A Target For Neurodegenerativmentioning

confidence: 99%

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

Liao

Dong

Cheng

2017

IJMS

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The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

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Modulation of mitochondrial calcium as a pharmacological target for Alzheimer's disease

Cited by 41 publications

References 115 publications

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina

Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina?

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

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