College of Arts & Sciences

Akash Bhat

College of Arts & Sciences

Biological Sciences

Faculty Mentor: Dr. Daniel R. Marenda Biology

Yianna Yiantsos Co-Mentor

Hereditary Spastic Paraplegia Treatment Drug Screen of TBCA

Hereditary Spastic Paraplegia (HSP) is an adult onset disease that causes progressive muscle weakness in the legs. HSP is most commonly caused by mutated spastin protein, an ATPase that cleaves microtubules in the axons of neurons. These microtubules are involved in the transport of intramolecular entities in neurons. Mutated spastin is seen to be less efficient in cleaving microtubules, limiting the growth of microtubules in axons. Two isoforms of spastin are seen in human neurons, M1 and M87. The most popular explanation for HSP is through haploinsufficiency, where axonal degeneration occurs due to a lack of spastin levels. However, this does not explain why HSP occurs in the adult. A possible explanation could be that the mutations of the M1 and M87 isoforms of spastin could be causing an upregulation of other factors that affect the motility of microtubules. The M1 isoform, found only in adult corticospinal cells, has been shown to have a stronger impact on the symptoms of HSP. TBCA, a CK2 inhibitor, is a drug that aids in microtubule stability. A drug screening of TBCA on fruit flies with human spastin could be used to see if any improvements occur and to determine an ideal concentration to use for future behavioral assays.