Abstract
The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts. By controlling the levels of synaptic proteins, adducin can de-stabilize synaptic contacts. Interestingly, elevated levels of phosphorylated adducin have been reported in ALS patients and in a mouse model of the disease. Adducin is regulated by phosphorylation through protein kinase C (PKC), some isoforms of which exhibit Ca2+-dependence, raising the possibility that changes in intracellular Ca2+ might alter PKC activation and secondarily influence adducin phosphorylation. Furthermore, adducin has interactions with the alpha subunit of the Na+/K+-ATPase. Thus, the phosphorylation of adducin may secondarily influence synaptic stability at the NMJ and so influence pre- and post-synaptic integrity at the NMJ in ALS.
Highlights
The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved
The neurodegenerative disorder amyotrophic lateral sclerosis (ALS), known as motor neurone disease (MND), is a motor system disease that causes progressive motoneuron loss in the spinal cord and brainstem leading to weakness and loss of muscle innervation, as well as the degeneration of descending motor tracts from the brain and subcortical structures resulting in spasticity (Eisen and Krieger, 2006; Su et al, 2014)
Gene mutations associated with familial ALS (FALS) have been under intense scrutiny, and such mutations are currently identified in approximately 50% of FALS patients
Summary
The neurodegenerative disorder amyotrophic lateral sclerosis (ALS), known as motor neurone disease (MND), is a motor system disease that causes progressive motoneuron loss in the spinal cord and brainstem leading to weakness and loss of muscle innervation (i.e., denervation), as well as the degeneration of descending motor tracts from the brain and subcortical structures resulting in spasticity (Eisen and Krieger, 2006; Su et al, 2014). At post-mortem, ALS patients have lost large numbers of spinal motoneurons, interneurons and other neuronal populations, but with considerable side-to-side asymmetry and variability at spinal and brain stem levels (Tsukagoshi et al, 1979; Swash et al, 1986). These findings are, by their very nature, end-stage effects and do not reflect the early stages of the disease. The large majority of ALS cases appear sporadically in the general population without evidence for an inherited gene mutation (‘‘sporadic ALS’’)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
