Abstract
Impaired energy homeostasis and aberrant translational control have independently been implicated in the pathogenesis of neurodegenerative diseases. AMP kinase (AMPK), regulated by the ratio of cellular AMP and ATP, is a major gatekeeper for cellular energy homeostasis. Abnormal regulation of AMPK has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Most importantly, AMPK activation is known to suppress the translational machinery by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), activating translational regulators, and phosphorylating nuclear transporter factors. In this review, we describe recent findings on the emerging role of protein translation impairment caused by energy dysregulation in neurodegenerative diseases.
Highlights
Despite the tremendous effort that has been devoted to the investigation of neurodegenerative diseases in the past decades, effective treatments remain limited
Dysregulated protein translation in neurodegenerative diseases may occur by a wide variety of complex mechanisms that lead to inferior ribosome biogenesis and poor protein synthesis efficiency
Interventions that enhance protein translation efficiency have been linked with improved neuronal plasticity and functions in many experimental models of neurodegenerative diseases
Summary
Despite the tremendous effort that has been devoted to the investigation of neurodegenerative diseases in the past decades, effective treatments remain limited. AD patients have abnormal phosphorylation levels of translational regulators (e.g., mTOR, 4E-BP1, eEF2K), suggesting aberrant protein synthesis.
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