A recent release shows scientists pulling together varied threads of research into a view of aging, changing metabolism and neuron death in neurodegenerative disease. A number of different age-related neurodegenerative diseases involve a diminishing population of specific, essential cells in a small part of the brain. Parkinson's disease is one, and Huntington's - examined in this article - is another.

Their new evidence ties a metabolic defect to the loss of neurons in the striatum, the brain's "movement control" region. That neurodegeneration leads to the uncontrollable "dance-like" movements characteristic of the fatal, genetic disorder.

The researchers suggest that the selective loss of cells occurs because some parts of the brain are much more vulnerable to changes in metabolism. They also propose that the reduction in metabolic efficiency with aging - due to general molecular wear and tear, or other age-related conditions resulting from molecular wear and tear - contributes to the prevalence of neurodegenerative conditions in the old. In other words, metabolic decline is a necessary precursor.

As metabolic function generally diminishes in older people, such a connection might explain why many neurodegenerative diseases--such as Lou Gehrig's, Alzheimer's, and Parkinson's diseases, for example--tend to emerge and worsen with age

In the case of Huntington's, that decline comes from a genetic error that appears to mess up mitochondrial function - the essential process by which the body generates energy to power cells - hence young people can suffer the condition if that error is severe enough.

The problem, they found, lay instead in fat cells known as brown adipose tissue (BAT). In rodents, BAT is the primary tissue that controls body temperature. When the brain signals that the body is cold, the gene called PGC-1a increases production of a protein in BAT that leads the cellular powerhouses known as mitochondria to generate heat instead of energy.

In the BAT of hypothermic Huntington's mice, PGC-1a levels rose but failed to elicit the other events required to maintain normal body temperature, they found.

The link to mitochondria-regulating PGC-1a led the team back to the brain, and specifically to the striatum. That brain region is most affected in Huntington's disease and is particularly sensitive to mitochondrial dysfunction.

The researchers found that tissue taken from striatums of Huntington's disease patients and mice showed reduced activity of genes controlled by PGC-1a. They further found reduced mitochondrial function in the brains of Huntington's mice.

While scientists continue to work on uncovering the first cause of age-related changes in the body, there are intermediate term strategies for treating people who suffer from these very specific neurodegenerative conditions. One such strategy is to develop the technology to use embryonic stem cells to grow replacement neurons for those small populations in decline:

Unlike normal somatic cells, human embryonic stem cells (hESCs) can proliferate indefinitely in culture in an undifferentiated state where they do not appear to undergo senescence and yet remain nontransformed. Cells maintain their pluripotency both in vivo and in vitro, exhibit high telomerase activity, and maintain telomere length after prolonged in vitro culture. Thus, hESCs may provide an unlimited cell source for replacement in a number of aging-related neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease as well as other neurological disorders including spinal cord injuries.

Taming and understanding embryonic stem cells is the key to the next generation of regenerative medicine: any tissue for replacement in the body, produced on demand in a precisely controlled fashion.

Technorati tags: regenerative medicine, stem cell research

Posted by Reason at October 28, 2006 9:40 AM | TrackBack (0)