Abstract
Aggregation and deposition of β-amyloid and/or tau protein are the key neuropathological features in neurodegenerative disorders such as Alzheimer’s disease (AD) and other tauopathies including frontotemporal dementia (FTD). The interaction between oxidative stress, mitochondrial dysfunction and the impairment of calcium ions (Ca2+) homeostasis induced by misfolded tau and β-amyloid plays an important role in the progressive neuronal loss occurring in specific areas of the brain. In addition to the control of bioenergetics and ROS production, mitochondria are fine regulators of the cytosolic Ca2+ homeostasis that induce vital signalling mechanisms in excitable cells such as neurons. Impairment in the mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU) or release through the Na+/Ca2+ exchanger may lead to mitochondrial Ca2+ overload and opening of the permeability transition pore inducing neuronal death. Recent evidence suggests an important role for these mechanisms as the underlying causes for neuronal death in β-amyloid and tau pathology. The present review will focus on the mechanisms that lead to cytosolic and especially mitochondrial Ca2+ disturbances occurring in AD and tau-induced FTD, and propose possible therapeutic interventions for these disorders.
Highlights
Neurodegenerative disorders, characterised by progressive neuronal loss in specific areas of the brain, nowadays represent one of the biggest medical and social challenges: very few therapeutic strategies are available to slow down the course of these diseases
The present review will focus on the mechanisms that lead to cytosolic and especially mitochondrial Ca2+ disturbances occurring in Alzheimer’s disease (AD) and tau-induced frontotemporal dementia (FTD), and propose possible therapeutic interventions for these disorders
The present review will focus on the Ca2+ signalling impairment, with a special emphasis on the mitochondrial Ca2+ dysbalance occurring in AD and tau-induced FTD
Summary
Neurodegenerative disorders, characterised by progressive neuronal loss in specific areas of the brain, nowadays represent one of the biggest medical and social challenges: very few therapeutic strategies are available to slow down the course of these diseases. Β-amyloid plaques found in Alzheimer’s disease (AD) and tau aggregates present in AD, frontotemporal dementia (FTD) and up to other 20 diseases collectively termed tauopathies are one of the most studied [1]. The interplay between oxidative stress, mitochondrial dysfunction and calcium ions (Ca2+ ) impairment has been shown to mediate neuronal dysfunction and death in patients’ cells and cellular and animal models of β-amyloid and tau pathology. The present review will focus on the Ca2+ signalling impairment, with a special emphasis on the mitochondrial Ca2+ dysbalance occurring in AD and tau-induced FTD
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