Assessing The Therapeutic Viability of Hsc70 in ALS
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- abstract
- Amyotrophic lateral sclerosis (ALS) is a rapid and fatal neurodegenerative disease, characterized by the denervation of the neuromuscular junction and death of motor neurons. When cells face stressful insult the heat shock response is activated in an attempt to reduce intracellular calamity. The heat shock response is identified by the increased expression of heat shock proteins (HSPs), which act as part of a chaperone network within the cell to combat an unfolded protein response. Motor neurons exhibit an aberrant heat shock response and do not upregulate the expression of Hsp70 under stressful conditions. Both intra- and extracellular events in ALS disease pathology contribute to cellular stress. We have previously shown that administration of recombinant human Hsp70 (rhHsp70) is protective to the survival of motor neurons and significantly delays denervation of the neuromuscular junction in the SOD1-G93A mouse model of ALS. The constitutively expressed iso-form of Hsp70 – Hsc70 – also promotes motor neuron survival in primary cultures. Unfortunately, the price of both commercially available proteins makes them cost prohibitive to study, thus acquiring them by different means is necessary for further investigation. Here we present a reliable protocol for the small-batch purification of rhHsc70 and examine its therapeutic viability in treating ALS.
- subject
- ALS
- Amyotrophic Lateral Sclerosis
- Heat Shock Protein 70
- Hsc70
- Motor Neuron
- Therapeutic
- contributor
- Ma, Tao (committee chair)
- Caress, James (committee member)
- date
- 2017-08-22T08:35:29Z (accessioned)
- 2019-08-21T08:30:13Z (available)
- 2017 (issued)
- degree
- Biomedical Science – MS (discipline)
- embargo
- 2019-08-21 (terms)
- identifier
- http://hdl.handle.net/10339/86353 (uri)
- language
- en (iso)
- publisher
- Wake Forest University
- title
- Assessing The Therapeutic Viability of Hsc70 in ALS
- type
- Thesis