Duchenne Muscular Dystrophy

Microtubules

Microtubules perform highly critical roles in the cell. If some perturbation happens, microtubules cannot function properly thus leads to diverse diseases in some tissue. In human body, the dysfunction of microtubules can cause many devastating diseases, for instance, Duchenne Muscular Dystrophy, Parkinson Disease, and Primary Ciliary Dyskinesia.

Duchenne Muscular Dystrophy (DMD) is a degenerative muscle disease, which caused by the increased production of oxidase dependent reactive oxygen species (X-ROS) and Ca2+ influx in the muscle cell (Khairallah et al., 2012). This increase of oxidative stress will proceed to the necrosis of muscle cells. Microtubules play an important role in regulating the mechano-activation of Ca2+ and RO S signaling pathways. The absence of dystrophin, a

This disease is induced by the loss of dopamine production from dopaminergic (DA) neurons. These neurons have long microtubules-enriched axons. Parkin, a microtubules-associated protein, binds strongly to the microtubules, and acts as a protein-ubiquitin E3 ligase that ubiquitinate misfolded proteins to be relocated to the cytosol, and to stabilize the microtubules. The mutation of gene that responsible of the production of parkin can cause the dissociation of parkin from microtubules, which leads to the depolymerization of microtubules. The free tubulin dimers from depolymerization will be ubiquitinated and degraded by the parkin protein (Figure 9). Microtubules degradation can induce the degradation of DA, which lowers the production of dopamine. The low production of dopamine can be treated with dopamine agonist. One of the drug that acts as dopamine agonist is levodopa (Fahn, 2008). Levodopa can be converted to dopamine in the brain, which replaces the depletion of dopamine in patients that have Parkinson