It is likely that DHT, not testosterone, is the ligand responsible for neuronal pathology in SBMA, given the high motor neuron levels of the testosterone-to-DHT converting enzyme 5α-reductase (Pozzi et al., 2003).
30 Utilizing the Cre-lox system, ChAT Cre mice have selectively reduced levels of SMN protein in motor neurons (levels produced by two copies of SMN2) in motor neurons and other cells have control levels of SMN.
Spinal muscular atrophy (SMA) is caused by low survival motor neuron (SMN) levels and patients represent a clinical spectrum due primarily to varying copies of the survival motor neuron-2 (SMN2) gene.
Even at symptomatic disease end stage GDNF was able to maintain over 30% of the motor neurons, a level which should be sufficient to prevent symptoms.
Among plastic effects, the sprouting of axon collaterals from spared motor neuron at the level of the peripheral muscles is well described [ 3, 4].
In peripheral nerves Schwann cells express high levels of TLRs, with TLR3 and -4 being the most prominent, whereas in sensory and motor neurons the levels are minimal [10].
SMA is the cascade of genetic deficits, resulting in the decrease of survival of motor neuron (SMN) protein levels.
Preclinical therapies that restore survival motor neuron (SMN) protein levels can dramatically extend survival in spinal muscular atrophy (SMA) mouse models.
Interruption of the spinothalamic fibres, which transmit sensory impulses from both sides of the body to the thalamus, causes a loss of light touch, temperature, and pain sensations, as well as signs of an upper motor neuron lesion below the level of the cavity.
