Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

Liu, Yu-Ju; Tsai, Andy Po‐Yi; Chern, Yijuang

doi:10.3389/fncel.2017.00126

Cited by 12 publications

(11 citation statements)

References 215 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly also, activation of AMPK changed the location of a mRNA stabilizer in the motor neurons of ALS patients, in mouse motor neurons, and in a motor neuron cell line, and this mislocalization was also suppressed by activation of A 2A Rs ( Liu et al, 2015b ). This again reinforces the idea of a putative neuroprotective role of A 2A Rs in ALS since impaired RNA homeostasis is a major pathway for ALS pathogenesis ( Liu et al, 2017 ).…”

Section: Introductionsupporting

confidence: 83%

Amyotrophic Lateral Sclerosis (ALS) and Adenosine Receptors

2018

View full text Add to dashboard Cite

In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS). Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing toward a beneficial role of A2A receptors (A2AR), most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signaling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression.

show abstract

Section: Introductionsupporting

confidence: 83%

Amyotrophic Lateral Sclerosis (ALS) and Adenosine Receptors

2018

View full text Add to dashboard Cite

show abstract

“…The pathophysiological mechanisms leading to the degeneration of motor neurons are still largely unknown and possibly multifactorial. However, there are several hypotheses underlying the disease process including oxidative stress, glutamate excitotoxicity, impaired mitochondrial function, aberrant protein folding, disturbances in RNA metabolism and impaired axonal transport ( Turner and Talbot, 2008 ; Wang et al, 2015 ; De Vos and Hafezparast, 2017 ; Liu and Tsai, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study

Weerasekera

Sima

Dresselaers

et al. 2018

NeuroImage: Clinical

View full text Add to dashboard Cite

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic intervention and disease management. To identify potential diagnostic markers, we investigated age-dependent effects of disease onset and progression on regional neurochemistry in the SOD1G93A ALS mouse model using localized in vivo magnetic resonance spectroscopy (MRS). We focused mainly on the brainstem region since brainstem motor nuclei are the primarily affected regions in SOD1G93A mice and ALS patients. In addition, metabolite profiles of the motor cortex were also assessed. In the brainstem, a gradual decrease in creatine levels were detected starting from the pre-symptomatic age of 70 days postpartum. During the early symptomatic phase (day 90), a significant increase in the levels of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) was measured. At later time points, alterations in the form of decreased NAA, glutamate, glutamine and increased myo-inositol were observed. Also, decreased glutamate, NAA and increased taurine levels were seen at late stages in the motor cortex. A proof-of-concept (PoC) study was conducted to assess the effects of coconut oil supplementation in SODG93A mice. The PoC revealed that the coconut oil supplementation together with the regular diet delayed disease symptoms, enhanced motor performance, and prolonged survival in the SOD1G93A mouse model. Furthermore, MRS data showed stable metabolic profile at day 120 in the coconut oil diet group compared to the group receiving a standard diet without coconut oil supplementation. In addition, a positive correlation between survival and the neuronal marker NAA was found. To the best of our knowledge, this is the first study that reports metabolic changes in the brainstem using in vivo MRS and effects of coconut oil supplementation as a prophylactic treatment in SOD1G93A mice.

show abstract

“…Specifically, increased production of pro‐inflammatory cytokines by circulating leucocytes was postulated to increase energy expenditure by mediating mitochondrial dysfunction . Separately, mitochondrial dysfunction independent of pro‐inflammatory processes has also been identified as an important pathophysiological mechanism in mediating dysregulation of metabolism in ALS . In addition, increased activity of adenosine monophosphate‐activated protein kinase, an energy sensor enzyme, has been reported in ALS and linked to dysregulation of energy homeostasis .…”

mentioning

confidence: 99%

“…Separately, mitochondrial dysfunction independent of pro‐inflammatory processes has also been identified as an important pathophysiological mechanism in mediating dysregulation of metabolism in ALS . In addition, increased activity of adenosine monophosphate‐activated protein kinase, an energy sensor enzyme, has been reported in ALS and linked to dysregulation of energy homeostasis . Of further relevance, cortical hyperexcitability has also been identified as an important pathophysiological mechanism in ALS , which could mediate hypermetabolism by increasing cortical glucose consumption.…”

mentioning

confidence: 99%