2022
DOI: 10.3389/fcell.2021.736267
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PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy

Abstract: As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impa… Show more

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Cited by 11 publications
(8 citation statements)
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“…After 24 h, 200 µL of ATP lysis solution was added to each well according to the instructions, and the ATP content was detected. At the same time, the total protein concentration was detected, and the ATP content per mg protein was compared [42].…”
Section: Intracellular Ros Content Pi Sod Gsh and Atp Assaysmentioning
confidence: 99%
“…After 24 h, 200 µL of ATP lysis solution was added to each well according to the instructions, and the ATP content was detected. At the same time, the total protein concentration was detected, and the ATP content per mg protein was compared [42].…”
Section: Intracellular Ros Content Pi Sod Gsh and Atp Assaysmentioning
confidence: 99%
“…Loss of PINK1 function is associated with cognitive/executive dysfunction in recessive familial PD (Li et al, 2005;Ricciardi et al, 2014;Piredda et al, 2020) and in sporadic AD and its mouse models (George et al, 2010;Du et al, 2017;Manczak et al, 2018;Jiang et al, 2021). Here, we demonstrate that loss of endogenous mouse PINK1 elicits dendritic simplification of 2).…”
Section: Discussionmentioning
confidence: 64%
“…Moreover, expression of wild-type (WT) PINK1 is reduced by chronic complex I inhibition in a model of environmental PD (Verma et al, 2020). Reduced PINK1 expression is also observed in the cortex of sporadic Alzheimer's disease (AD) patients (George et al, 2010;Du et al, 2017) and in mouse models of AD (George et al, 2010;Du et al, 2017;Manczak et al, 2018), whereas restoring PINK1 expression ameliorates AD pathology and cognitive dysfunction in vivo (Du et al, 2017;Jiang et al, 2021). Together, these studies suggest that reduced PINK1 function contributes to cognitive impairment, yet the underlying substrate for this deficit is unclear.…”
Section: Introductionmentioning
confidence: 99%
“…It is believed that changes in mitochondrial dynamics affect almost all aspects of mitochondrial function, including energy metabolism, calcium buffering, ROS generation, and apoptosis (Zhu et al., 2013). While wild‐type full‐length tau had the capacity to stabilize microtubules, its over‐expression led to an accumulation of tau in mitochondria, disrupting mitochondrial dynamics, inhibiting mitophagy, and ultimately resulting in mitochondrial dysfunction (Herzmann et al., 2017; Hu et al., 2016; Jiang et al., 2021; Li et al., 2016). Among the three tau forms, TauKQ is the most toxic, as evidenced by a more severe membrane potential collapse, more decreased ATP, and increased ROS levels.…”
Section: Discussionmentioning
confidence: 99%