Dietary restriction supports peripheral nerve health by enhancing endogenous protein quality control mechanisms

Lee, Sooyeon; Notterpek, Lucia

doi:10.1016/j.exger.2012.12.008

Cited by 36 publications

(24 citation statements)

References 49 publications

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“…PMP22-linked hereditary neuropathies fall in this category as Schwann cells of affected nerves contain ubiquitin-positive protein aggregates and markers of elevated basal autophagy (Fortun et al, 2003, Fortun et al, 2006). Activation of autophagy by dietary modulation has been shown to be beneficial in animal models of protein aggregation disorders, including Alzheimer’s and Parkinson’s diseases, as well as CMT1A neuropathies (Madorsky et al, 2009, Srivastava and Haigis, 2011, Lee and Notterpek, 2013). Through inhibition of mTOR, a well-known regulator of autophagy, rapamycin is considered to be a calorie restriction mimetic and is of great interest in studies of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice

Nicks

Lee

Harris

et al. 2014

Neurobiology of Disease

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Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy characterized by progressive demyelination and distal muscle weakness. Abnormal expression of peripheral myelin protein 22 (PMP22) has been linked to CMT1A and is modeled by Trembler J (TrJ) mice, which carry the same leucine to proline substitution in PMP22 as affected pedigrees. Pharmacologic modulation of autophagy by rapamycin in neuron-Schwann cell explant cultures from neuropathic mice reduced PMP22 aggregate formation and improved myelination. Here we asked whether rapamycin administration by food supplementation, or intraperitoneal injection, could alleviate the neuropathic phenotype of affected mice and improve neuromuscular performance. Cohorts of male and female wild type (Wt) and TrJ mice were assigned to placebo or rapamycin treatment starting at 2 or 4 months of age and tested monthly on the rotarod. While neither long-term feeding (8 or 10 months) on rapamycin-enriched diet, or short term injection (2 months) of rapamycin improved locomotor performance of the neuropathic mice, both regimen benefited peripheral nerve myelination. Together, these results indicate that while treatment with rapamycin benefits the myelination capacity of neuropathic Schwann cells, this intervention does not improve neuromuscular function. The observed outcome might be the result of the differential response of nerve and skeletal muscle tissue to rapamycin.

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Section: Discussionmentioning

confidence: 99%

Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice

Nicks

Lee

Harris

et al. 2014

Neurobiology of Disease

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“…Rats maintained on energy-restricted diets exhibit reduced accumulation of polyubiquitinated proteins and evidence of increased autophagy in peripheral nerves compared with rats fed ad libitum (72). In a mouse model of CharcotMarie-Tooth type 1A, an inherited disorder characterized by demyelination of peripheral nerves, IER improved motor performance and reduced demyelination by a mechanism involving enhanced autophagy and reduced accumulation of myelin protein PMP22 aggregates (73).…”

Section: Cellular and Molecular Mechanisms: Insight From Intermittentmentioning

confidence: 98%

Meal frequency and timing in health and disease

Mattson

Allison

Fontana

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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463

359

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Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population. metabolism | circadian rhythm | time-restricted feeding | feeding behavior | obesity

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“…In a mouse model of the peripheral demyelinating neuropathic disease Charcot-Marie-tooth type 1A (Trembler mice), 5 months of ADF resulted in improved motor performance, increased myeli-nation and decreased accumulation of PMP22 protein aggregates (Madorsky et al, 2009). Additional findings suggest that the beneficial effects of IF on peripheral nerve health and disease resistance are mediated, in part, by up-regulation of autophagy and related protein quality control mechanisms (Lee and Notterpek, 2013). …”

Section: If and Health Indicators In Laboratory Animalsmentioning

confidence: 99%

Impact of intermittent fasting on health and disease processes

Mattson

Longo

Harvie

2017

Ageing Research Reviews

862

621

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Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16–48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease Parkinson’s disease and stroke. Studies of IF (e.g., 60% energy restriction on 2 days per week or every other day), PF (e.g., a 5 day diet providing 750–1100 kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8 h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.

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Dietary restriction supports peripheral nerve health by enhancing endogenous protein quality control mechanisms

Cited by 36 publications

References 49 publications

Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice

Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice

Meal frequency and timing in health and disease

Impact of intermittent fasting on health and disease processes

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