Welcome to Rejuvenation Science®!

 Questions? Please call us at
1-888-737-3588 TOLL FREE

Mitochondrial Dysfunction Associated With Alzheimer's Disease

Researchers have provided new information about how communication among neurons may be prevented from deteriorating in conditions such as Alzheimer’s disease (AD). The new results, which appear in the August 2007 issue of Molecular & Cellular Proteomics, may lead to new therapies for the treatment of not only AD but also motor neuron diseases and prion diseases.

Most current research efforts to find a treatment for Alzheimer's Disease and similar conditions focuses on what happens to the main part – or body – of a neuron, but recent studies have examined how neuronal communication is impaired in human diseases such as AD. When a neuron interacts with another neuron, it uses an extension called an axon that releases chemicals, which diffuse across a tiny gap between the neurons called a synapse and crosses the other neuron. Deterioration of synapses and axons can be delayed thanks to a protein created by a gene called the slow Wallerian degeneration (Wlds) gene. How this protein works is still a mystery, but it may lead to new therapies for the treatment of AD and other conditions.

Thomas H. Gillingwater and colleagues identified 16 proteins that are affected by the Wlds gene. Although details are still missing, Wlds probably prevents these proteins from deteriorating synapses and axons. The scientists found that some of the proteins had previously been shown to deteriorate synapses and axons, but, unexpectedly, eight proteins regulate the function of mitochondria – cellular organelles that supply energy to cells. These results reveal for the first time that mitochondria are involved in the protection of neurons provided by the Wlds gene and suggest that targeting some of the proteins identified in this study may lead to novel therapies for the treatment of AD, motor neuron diseases, and prion diseases.

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at www.asbmb.org.


Non-somatic synaptic and axonal compartments of neurons are primary pathological targets in many neurodegenerative conditions, ranging from Alzheimer disease through to motor neuron disease. Axons and synapses are protected from degeneration by the slow Wallerian degeneration (Wlds) gene. Significantly the molecular mechanisms through which this spontaneous genetic mutation delays degeneration remain controversial, and the downstream protein targets of Wlds resident in non-somatic compartments remain unknown. In this study we used differential proteomics analysis to identify proteins whose expression levels were significantly altered in isolated synaptic preparations from the striatum of Wlds mice. Eight of the 16 proteins we identified as having modified expression levels in Wlds synapses are known regulators of mitochondrial stability and degeneration (including VDAC1, Aralar1, and mitofilin). Subsequent analyses demonstrated that other key mitochondrial proteins, not identified in our initial screen, are also modified in Wlds synapses. Of the non-mitochondrial proteins identified, several have been implicated in neurodegenerative diseases where synapses and axons are primary pathological targets (including DRP-2 and Rab GDP dissociation inhibitor ß). In addition, we show that downstream protein changes can be identified in pathways corresponding to both Ube4b (including UBE1) and Nmnat1 (including VDAC1 and Aralar1) components of the chimeric Wlds gene, suggesting that full-length Wlds protein is required to elicit maximal changes in synaptic proteins.

We conclude that altered mitochondrial responses to degenerative stimuli are likely to play an important role in the neuroprotective Wlds phenotype and that targeting proteins identified in the current study may lead to novel therapies for the treatment of neurodegenerative diseases in humans.


Thomas M. Wishart, Janet M. Paterson, Duncan M. Short, Sara Meredith, Kevin A. Robertson, Calum Sutherland, Michael A. Cousin, Mayank B. Dutia, and Thomas H. Gillingwater. Differential Proteomics Analysis of Synaptic Proteins Identifies Potential Cellular Targets and Protein Mediators of Synaptic Neuroprotection Conferred by the Slow Wallerian Degeneration (Wlds) Gene; Mol Cell Proteomics 2007 Aug 6: 1318-1330. (http://www.mcponline.org)

Press Release, Aug 22, 2007, American Society for Biochemistry and Molecular Biology (ASBMB)

Key concepts: migraine headache, CVD, cardiovascular disease, mitochondrial function,