Calcium and neurodegeneration

HD Lighthouse Contributing Editor's Comment: 

This helpful review essay explains why calcium is so important to neuronal functioning and how it is dysregulated in neurodegenerative disorders such as Huntington's Disease, in stroke and, more subtly, in normal aging.

Neurons communicate with one another through electrochemical symptoms.   

While researchers work on discovering or developing drugs to maintain calcium homeostasis, is there anything that individuals with the HD gene can do to help themselves right now? Mattson reviews some indirect animal evidence which suggests that exercise, cognitive stimulation, dietary energy restriction may help. and

The likely mechanism here is that exercise, cognitive stimulation and dietary energy restriction create mild stress for the neuron which activates various kinases. These kinases in turn activate or suppress various transcription factors resulting in the expression or suppression of certain genes. The end result is that the neuron's adaptive responses are increased and it is better prepared to deal with the more serious stress presented by stroke or diseases like Huntington's, Parkinson's and Alzheimer's.

In addition, a diet which is heart healthy and rich in antioxidants should also be helpful.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 05-28-2008

Mark P. Mattson, Ph.D., Senior Investigator Chief, Laboratory of Neurosciences and Chief, Cellular and Molecular Neurosciences Section

Mark P. Mattson

When properly controlled, Ca2+ fluxes across the plasma membrane and between intracellular compartments play critical roles in fundamental functions of neurons, including the regulation of neurite outgrowth and synaptogenesis, synaptic transmission and plasticity, and cell survival.

During aging, and particularly in neurodegenerative disorders, cellular Ca2+-regulating systems are compromised resulting in synaptic dysfunction, impaired plasticity and neuronal degeneration. Oxidative stress, perturbed energy metabolism and aggregation of disease-related proteins (amyloid β-peptide, α-synuclein, huntingtin, etc.) adversely affect Ca2+ homeostasis by mechanisms that have been elucidated recently. Alterations of Ca2+-regulating proteins in the plasma membrane (ligand- and voltage-gated Ca2+ channels, ion-motive ATPases, and glucose and glutamate transporters), endoplasmic reticulum (presenilin-1, Herp, and ryanodine and inositol triphosphate receptors), and mitochondria (electron transport chain proteins, Bcl-2 family members, and uncoupling proteins) are implicated in age-related neuronal dysfunction and disease.

The adverse effects of aging on neuronal Ca2+ regulation are subject to modification by genetic (mutations in presenilins, α-synuclein, huntingtin, or Cu/Zn-superoxide dismutase; apolipoprotein E isotype, etc.) and environmental (dietary energy intake, exercise, exposure to toxins, etc.) factors that may cause or affect the risk of neurodegenerative disease. A better understanding of the cellular and molecular mechanisms that promote or prevent disturbances in cellular Ca2+ homeostasis during aging may lead to novel approaches for therapeutic intervention in neurological disorders such as Alzheimer's and Parkinson's diseases and stroke.

Source: Aging Cell Volume 6 Issue 3 Page 337-350, June 2007