Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Liu, Yu-Ju; Chern, Yijuang

doi:10.3389/fncel.2021.668500

Cited by 11 publications

(5 citation statements)

References 145 publications

(169 reference statements)

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“…Impaired protein synthesis is a molecular event that occurs in neurodegeneration and that has been shown to have a link with the aggregation of unfolded proteins [ 156 ]. This deficit can in turn result in defective synapse transmission and organelle transportation [ 157 ].…”

Section: Discussionmentioning

confidence: 99%

Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1

Masi

Attanzio

Racchi

et al. 2022

Cells

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The role of protein misfolding, deposition, and clearance has been the dominant topic in the last decades of investigation in the field of neurodegeneration. The impairment of protein synthesis, along with RNA metabolism and RNA granules, however, are significantly emerging as novel potential targets for the comprehension of the molecular events leading to neuronal deficits. Indeed, defects in ribosome activity, ribosome stalling, and PQC—all ribosome-related processes required for proteostasis regulation—can contribute to triggering stress conditions and promoting the formation of stress granules (SGs) that could evolve in the formation of pathological granules, usually occurring during neurodegenerating effects. In this review, the interplay between proteostasis, mRNA metabolism, and SGs has been explored in a neurodegenerative context with a focus on Alzheimer’s disease (AD), although some defects in these same mechanisms can also be found in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are discussed here. Finally, we highlight the role of the receptor for activated C kinase 1 (RACK1) in these pathologies and note that, besides its well characterized function as a scaffold protein, it has an important role in translation and can associate to stress granules (SGs) determining cell fate in response to diverse stress stimuli.

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Section: Discussionmentioning

confidence: 99%

Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1

Masi

Attanzio

Racchi

et al. 2022

Cells

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“…The clinical interest in MTF-based therapy has been recently expanded to include several neurological disorders, mainly because of the parallel between some neuropathological mechanisms recognized in both types of diabetes (type 1 and type 2) and neurodegenerative diseases such as Alzheimer’s disease [ 52 ]. Indeed, energy dysfunction, failure in AMPK activation and disinhibition of mTORC1 signaling are mechanisms accountable for the deficit in protein translation underlying neurodegeneration [ 52 ] as well as for the relationship between stimulation of autophagy machinery, MTF treatment and relief from NeP [ 53 ]. The sex-dependent assessment of MTF-induced AMPK phosphorylation revealed a lack of AMPK activation in female mice, while at D3, after CCI, we found the highest degree of AMPK activation in male animals, which was still higher at D7.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Neuropathy: The Paradigmatic Case of MetFormin

Angelis

Vacca

Tofanicchio

et al. 2022

IJMS

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As a widely prescribed anti-diabetic drug, metformin has been receiving novel attention for its analgesic potential. In the study of the complex etiology of neuropathic pain (NeP), male and female individuals exhibit quite different responses characterized by higher pain sensitivity and greater NeP incidence in women. This “gender gap” in our knowledge of sex differences in pain processing strongly limits the sex-oriented treatment of patients suffering from NeP. Besides, the current investigation of the analgesic potential of metformin has not addressed the “gender gap” problem. Hence, this study focuses on metformin and sex-dependent analgesia in a murine model of NeP induced by chronic constriction injury of the sciatic nerve. We investigated sexual dimorphism in signaling pathways involved by 7 days of metformin administration, such as changes in AMP-activated protein kinase and the positive regulation of autophagy machinery, discovering that metformin affected in a sexually dimorphic manner the immunological and inflammatory response to nerve lesion. These effects were complemented by morphological and adaptive changes occurring after peripheral nerve injury. Altogether these data can contribute to explaining a number of potential mechanisms responsible for the complete recovery from NeP found in male mice, as opposed to the failure of long-lasting recovery in female animals.

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“…Activation of SnRK1, a key sensor of energy stress signaling, results in convergent reprogramming of the transcriptome and global metabolism to adapt to and survive such cellular energy crises [ 24 , 25 ]. In mammalian cells, AMPK-mediated translational inhibition and its regulatory mechanism have been reported at multiple steps [ 26 ]. However, the SnRK1-mediated translational regulation mechanism remains to be elucidated largely in plants.…”

Section: Discussionmentioning

confidence: 99%

SNF1-Related Protein Kinase 1 Activity Represses the Canonical Translational Machinery

Son

Song

et al. 2022

Plants

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Protein biosynthesis is achieved through translation, which consumes enormous energy. Therefore, under conditions of limited energy supply, translation progress should be strictly coordinated. Sucrose non-fermenting kinase1 (SNF1)-related protein kinase 1 (SnRK1) is an evolutionarily conserved master regulator of cellular energy stress signaling in plants. Rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana) SnRK1 enhance hypoxia tolerance and induce the expression of stress-related genes. However, whether SnRK1 modulates protein synthesis in plants is unknown. In this study, using translational reporter constructs transfected in Arabidopsis protoplasts we showed that the expression of OsSnRK1A and AtSnRK1.1 decreases the abundance of canonical proteins without affecting their encoding transcript levels and protein stability. Moreover, the loading of total mRNAs and GFP mRNAs into the heavy polysome fraction which is normally translated was attenuated in transgenic Arabidopsis lines constitutively expressing OsSnRK1A or AtSnRK1.1. Taken together, these results suggest that OsSnRK1A and AtSnRK1.1 suppress protein translation to maintain energy homeostasis.

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Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Cited by 11 publications

References 145 publications

Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1

Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1

Sex Differences in Neuropathy: The Paradigmatic Case of MetFormin

SNF1-Related Protein Kinase 1 Activity Represses the Canonical Translational Machinery

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