High-energy compounds mobilize intracellular Ca2+ and activate calpain in cultured cells: Is calpain an energy-dependent protease?

Nguyen, Huey T.; Chen, Ming

doi:10.1016/j.brainresbull.2014.01.006

Cited by 2 publications

(1 citation statement)

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“…As such, numerous energy-promoting and Ca 2+ -activating agents/practices would be useful. These include but are not limited to: physical exercise, glucose catabolism stimulators, energy-rich substances, growth factors, hormones, neurotransmitter receptor agonists, neurotrophic factors, and metabolic enhancers ( Nguyen et al, 2013 ; Nguyen and Chen, 2014 ).…”

Section: A Broad New Frontier For Sad Preventionmentioning

confidence: 99%

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

Chen

Nguyen

2014

Front. Aging Neurosci.

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Sporadic Alzheimer’s disease (sAD) has not been explained by any current theories, so new hypotheses are urgently needed. We proposed that “energy and Ca2+ signaling deficits” are perhaps the earliest modifiable defects in brain aging underlying memory decline and tau deposits (by means of inactivating Ca2+-dependent protease calpain). Consistent with this hypothesis, we now notice that at least eight other known calpain substrates have also been reported to accumulate in aging and AD. Thus, protein accumulation or aggregation is not a “pathogenic” event, but occurs naturally and selectively to a peculiar family of proteins, and is best explained by calpain inactivation. Why are only calpain substrates accumulated and how can they stay for decades in the brain without being attacked by many other non-specific proteases there? We believe that these long-lasting puzzles can be explained by calpain’s unique properties, especially its unusual specificity and exclusivity in substrate recognition, which can protect the substrates from other proteases’ attacks after calpain inactivation. Interestingly, our model, in essence, may also explain tau phosphorylation and the formation of amyloid plaques. Our studies suggest that α-secretase is an energy-/Ca2+-dual dependent protease and is also the primary determinant for Aβ levels. Therefore, β- and γ-secretases can only play secondary roles and, by biological laws, they are unlikely to be “positively identified”. This study thus raises serious questions for policymakers and researchers and these questions may help explain why sAD can remain an enigma today.

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Section: A Broad New Frontier For Sad Preventionmentioning

confidence: 99%

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

Chen

Nguyen

2014

Front. Aging Neurosci.

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N -methyl- d -aspartate receptor-mediated calcium overload and endoplasmic reticulum stress are involved in interleukin-1beta-induced neuronal apoptosis in rat hippocampus

Dong

Kalueff

Song

2017

Journal of Neuroimmunology

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High-energy compounds mobilize intracellular Ca2+ and activate calpain in cultured cells: Is calpain an energy-dependent protease?

Cited by 2 publications

References 32 publications

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

N -methyl- d -aspartate receptor-mediated calcium overload and endoplasmic reticulum stress are involved in interleukin-1beta-induced neuronal apoptosis in rat hippocampus

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High-energy compounds mobilize intracellular Ca2+ and activate calpain in cultured cells: Is calpain an energy-dependent protease?

Cited by 2 publications

References 32 publications

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

N -methyl- d -aspartate receptor-mediated calcium overload and endoplasmic reticulum stress are involved in interleukin-1beta-induced neuronal apoptosis in rat hippocampus

Contact Info

Product

Resources

About

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease

Our â€œenergy-Ca2+ signaling deficitsâ€ hypothesis and its explanatory potential for key features of Alzheimerâ€™s disease