Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase‐3β

Kitazawa, Masashi; Trinh, Dan N.; LaFerla, Frank M.

doi:10.1002/ana.21325

Cited by 78 publications

(59 citation statements)

References 40 publications

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“…130 This tau-clearing effect of lithium was recently reported to be beneficial beyond the field of interest of ALS by producing symptomatic and pathologic relief in a transgenic mouse model of inclusion body myositis. 131 Furthermore, several beneficial effects of lithium have also been described in a Drosophila model of Alzheimer's disease (AD). This model expresses a mutant form of tau, which induced locomotor dysfunction and vesicular aggregations, and lithium was able to reverse altered axonal transport and improve locomotor impairment by inhibiting GSK-3beta.…”

Section: Beyond Autophagymentioning

confidence: 99%

Autophagy, lithium, and amyotrophic lateral sclerosis

et al. 2009

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In this article we provide an overview of the intersection between amyotrophic lateral sclerosis (ALS) and the autophagy pathway and discuss the potential protective effects of lithium through mechanisms that recruit autophagy and other effects. The autophagy pathway is recruited during motor neuron (MN) death both in vitro and in vivo. Despite a few controversial issues concerning the significance (detrimental/protective) of autophagy in ALS, recent findings indicate a protective role. Lithium in low doses is a well-known autophagy inducer that clears misfolded proteins and altered mitochondria from MNs. Moreover, lithium preserves mitochondria and sustains their genesis. This effect is replicated by rapamycin, which is an autophagy inducer but with a different mechanism from lithium. Lithium also increases the number of Renshaw cells that are affected early during the progression of experimental ALS. Again, lithium has been reported to decrease glial proliferation in the ALS spinal cord and induces sprouting in corticospinal fibers. Muscle Nerve 40: 173-194, 2009.

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Section: Beyond Autophagymentioning

confidence: 99%

Autophagy, lithium, and amyotrophic lateral sclerosis

et al. 2009

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“…It has been demonstrated that defective mitochondrial function leads to Aβ accumulation [42]. Moreover, inflammation significantly increases Aβ accumulation, leading to muscle impairment [43]. Thus, further studies in a CQ-induced s-IBM rat model should clarify the effects of RE on these molecular mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis

2019

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Background: Mitochondrial dysfunction is implicated in the pathogenesis of multiple muscular diseases, including sporadic inclusion body myositis (s-IBM), the most common aging-related muscle disease. However, the factors causing mitochondrial dysfunction in s-IBM are unknown. Objective: We hypothesized that resistance exercise (RE) may alleviate muscle impairment by improving mitochondrial function via reducing amyloid-beta (Aβ) accumulation. Methods: Twenty-four male Wistar rats were randomized to a saline-injection control group (sham, n = 8), a chloroquine (CQ) control group (CQ-CON, n = 8), and a CQ plus RE group (CQ-RE, n = 8) in which rats climbed a ladder with weight attached to their tails 9 weeks after starting CQ treatment. Results: RE markedly inhibited soleus muscle atrophy and muscle damage. RE reduced CQ-induced Aβ accumulation, which resulted in decreased formation of rimmed vacuoles and mitochondrial-mediated apoptosis. Most importantly, the decreased Aβ accumulation improved both mitochondrial quality control (MQC) through increased mitochondrial biogenesis and mitophagy, and mitochondrial dynamics. Furthermore, RE-mediated reduction of Aβ accumulation elevated mitochondrial oxidative capacity by upregulating superoxide dismutase-2, catalase, and citrate synthase via activating sirtuin 3 signaling. Conclusion: RE enhances mitochondrial function by improving MQC and mitochondrial oxidative capacity via reducing Aβ accumulation, thereby inhibiting CQ-induced muscle impairment, in a rat model of s-IBM.

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“…Cytoplasmic hyperphosphorylated tau tangles in AD brains consist predominantly of 15–21 nm long paired helical filaments (PHF) 201. Similarly, in IBM muscle, accumulations of hyperphosphorylated tau‐containing PHF are observed and kinases such as extracellular signal‐regulated kinase (ERK) or GSK3 β , which have been reported to phosphorylate tau, are increased and colocalized with tau in IBM muscle fibers 206, 207, 208, 209, 210…”

Section: Degenerative Pathomechanisms In Ibmmentioning

confidence: 99%

Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

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Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.

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Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase‐3β

Abstract: Our results identify a molecular mechanism by which proinflammatory stimuli affect tau pathology via the GSK-3beta signaling pathway in skeletal muscle.

Cited by 78 publications

References 40 publications

Autophagy, lithium, and amyotrophic lateral sclerosis

Autophagy, lithium, and amyotrophic lateral sclerosis

Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis

Immune and myodegenerative pathomechanisms in inclusion body myositis

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