Significance of Small Heat Shock Proteins HSPB1 and HSPB5 in Aggregation and Degradation of Amyloid Proteins

Hdl Handle:
http://hdl.handle.net/10675.2/552945
Title:
Significance of Small Heat Shock Proteins HSPB1 and HSPB5 in Aggregation and Degradation of Amyloid Proteins
Authors:
Ojha, Juhi
Abstract:
Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Ap) aggregates and its deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of aB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that aB-crystallin protects cells against Ap toxicity. To test this, we crossed aB-crystallin/HspB2 deficient (CRYAB'A HSPB2'A) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions - (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning and (iii) evoked behavioral response was tested by hot plate method. Interestingly, aB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases.
Affiliation:
Not Listed
Issue Date:
10-Jun-2011
URI:
http://hdl.handle.net/10675.2/552945
Additional Links:
http://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/889026197?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorOjha, Juhien
dc.date.accessioned2015-05-15T14:55:01Zen
dc.date.available2015-05-15T14:55:01Zen
dc.date.issued2011-06-10en
dc.identifier.urihttp://hdl.handle.net/10675.2/552945-
dc.description.abstractMolecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Ap) aggregates and its deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of aB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that aB-crystallin protects cells against Ap toxicity. To test this, we crossed aB-crystallin/HspB2 deficient (CRYAB'A HSPB2'A) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions - (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning and (iii) evoked behavioral response was tested by hot plate method. Interestingly, aB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases.en
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/889026197?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectAlzheimer Diseaseen
dc.subjectCrystallinen
dc.subjectHeat-shock Proteinen
dc.subjectMemoryen
dc.subjectMiceen
dc.subjectPlaque, Amyloiden
dc.subjectProteostasis Deficienciesen
dc.titleSignificance of Small Heat Shock Proteins HSPB1 and HSPB5 in Aggregation and Degradation of Amyloid Proteinsen
dc.typeDissertationen
dc.contributor.departmentNot Listeden
dc.description.advisorNot Listeden
dc.description.committeeNot Listeden
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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