AbstractSpinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease, is a late onset motor neuron disease (MND) caused by an abnormal expansion of the CAG repeat in the androgen receptor (AR) gene on the X-chromosome, encoding a polyglutamine sequence (poly-Q) in the protein product. Mutant poly-Q expanded AR protein is widely expressed but leads to selective lower motoneuron death. Although the mechanisms that underlie SBMA remain unclear, defective axonal transport has been implicated in MND and other forms of poly-Q disease. Transcriptional dysregulation may also be involved in poly-Q repeat pathology. We therefore examined axonal transport in a mouse model of SBMA recapitulating many aspects of the human disease. We found no difference in the expression levels of motor and the microtubule associated protein tau, in spinal cord and sciatic nerve of wild-type (WT) and SBMA mice at various stages of disease progression. Furthermore, we found no alteration in binding properties of motor proteins and tau to microtubules. Moreover, analysis of axonal transport rates both in cultured primary motoneurons in vitro and in vivo in the sciatic nerve of adult WT and mutant SBMA mice, demonstrated no overt axonal transport deficits in these systems. Our results therefore indicate that unlike other motoneuron and poly-Q diseases, axonal transport deficits do not play a significant role in the pathogenesis of SBMA.
After reading the above, I asked our biology professor for a translation. As usual, he did a great job in explaining how the process works and what this research meant.
“There has been speculation that the reason that the motor neurons die in Kennedy’s Disease is that the transport of materials to the end of the axon is blocked. The motor neurons are the cells that tell muscle to contract. They have a cell body (main part of cell with all the usual cell parts) is in the spinal cord. Each cell also has a long tube-like process called an axon that connects to the muscle cell. Thus, the axon is a long continuation of the motor neuron - it is very long and thin (can be over 2-3 feet long in some instances). Since the cell body is where the cell machinery exists, the cell must be able to transport needed chemicals to the end of the axon - this is axonal transport. If this transport were to be blocked, then the axon, and thus the cell, would no longer function. This paper apparently has evidence that this axonal transport is NOT defective in Kennedy’s Disease.”
I am not certain how this helps, but I am certain that it might be beneficial for researchers in their work. The better we understand what works and what doesn’t has to be helpful as they search for a treatment.