{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/648"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/648","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"An Insight into Alpha-Synulcien's Biological Function and Its Pathogenesis in Neurodegenerative Disease","abstract":"The discovery of two missense mutations (A53T and A30P) in alpha -synuclein that are genetically linked to Parkinson's disease, together with alpha -synuclein being the major component in Lewy bodies, has generated extensive interest in alpha -synuclein as a key component in neurodegenerative diseases. In recent years modeling this disease in transgenic mice and flies has lead to new understandings of alpha -synuclein function and pathogenesis in neurodegeneration. In the current study we analyzed transgenic mice overexpressing human alpha -synuclein and human alpha -synuclein mutations (A53T&A30P) to; First establish these transgenic mice as a model for degenerative diseases; second to identify potential contributing factors in neurodegeneration; third to decipher a potential function of alpha -synuclein. We first established that transgenic mice expressing human variants of alpha -synuclein developed an age dependant motor dysfunction with symptom logy characteristic of Parkinson's disease. Immunohistological studies revealed the presence of alpha -synuclein inclusions and a loss of motor neurons. Biochemical analysis identified a 4-5 fold increase in ubiquitin with altered expression of proteasomal subunits, characteristic of proteasomal impairment. In addition, we identified a significant increase in amyloid beta -peptides. Protein quantification of apolipoprotein E (ApoE) a protein that has been associated with the development of Alzheimer's disease, demonstrated a 5-15 fold increase in symptomatic transgenic mice. Ablation of ApoE in alpha -synuclein transgenic mice by genetic crosses revealed a delayed onset for motor dysfunction and an overall increase in survival. ApoE deficient transgenic mice displayed a decrease in ubiquitin and amyloid beta -peptides. This study illustrates ApoE, ubiquitin and Abeta - peptides contribute to the onset and progression of the neurodegeneration in transgenic alpha -synuclein mice. Genetic crosses of transgenic alpha -synuclein with a csystine string protein-alpha (CSPalpha ) knockout mouse revealed a potential function for alpha -synuclein. CSPalpha deficient mice develop an early age neurodegenerative disease that is lethal at 3-4 months. Transgenic expression of human alpha -synuclein prevented the deleterious effects of CSPalpha deficiency. Immunofluorescence studies illustrated alpha -synuclein function in a cell autonomous manner. Biochemical analysis demonstrated CSPalpha deficient mice have impaired SNARE complexes that are partially reverted by transgenic alpha -synuclein. This study illustrates a protective function of alpha -synuclein in preventing neurodegeneration.","abstract_html":"The discovery of two missense mutations (A53T and A30P) in alpha -synuclein that are genetically linked to Parkinson's disease, together with alpha -synuclein being the major component in Lewy bodies, has generated extensive interest in alpha -synuclein as a key component in neurodegenerative diseases. In recent years modeling this disease in transgenic mice and flies has lead to new understandings of alpha -synuclein function and pathogenesis in neurodegeneration. In the current study we analyzed transgenic mice overexpressing human alpha -synuclein and human alpha -synuclein mutations (A53T&A30P) to; First establish these transgenic mice as a model for degenerative diseases; second to identify potential contributing factors in neurodegeneration; third to decipher a potential function of alpha -synuclein. We first established that transgenic mice expressing human variants of alpha -synuclein developed an age dependant motor dysfunction with symptom logy characteristic of Parkinson's disease. Immunohistological studies revealed the presence of alpha -synuclein inclusions and a loss of motor neurons. Biochemical analysis identified a 4-5 fold increase in ubiquitin with altered expression of proteasomal subunits, characteristic of proteasomal impairment. In addition, we identified a significant increase in amyloid beta -peptides. Protein quantification of apolipoprotein E (ApoE) a protein that has been associated with the development of Alzheimer's disease, demonstrated a 5-15 fold increase in symptomatic transgenic mice. Ablation of ApoE in alpha -synuclein transgenic mice by genetic crosses revealed a delayed onset for motor dysfunction and an overall increase in survival. ApoE deficient transgenic mice displayed a decrease in ubiquitin and amyloid beta -peptides. This study illustrates ApoE, ubiquitin and Abeta - peptides contribute to the onset and progression of the neurodegeneration in transgenic alpha -synuclein mice. Genetic crosses of transgenic alpha -synuclein with a csystine string protein-alpha (CSPalpha ) knockout mouse revealed a potential function for alpha -synuclein. CSPalpha deficient mice develop an early age neurodegenerative disease that is lethal at 3-4 months. Transgenic expression of human alpha -synuclein prevented the deleterious effects of CSPalpha deficiency. Immunofluorescence studies illustrated alpha -synuclein function in a cell autonomous manner. Biochemical analysis demonstrated CSPalpha deficient mice have impaired SNARE complexes that are partially reverted by transgenic alpha -synuclein. This study illustrates a protective function of alpha -synuclein in preventing neurodegeneration.","abstract_has_math":false,"creators":["Gallardo, Gilbert"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Südhof, Thomas C."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T18:43:53Z","date_published":"2010-07-12T18:43:53Z","updated_at":"2026-07-24T05:52:38Z","subjects":["alpha-Synuclein","Neurodegenerative Diseases","Amyloid beta-Protein"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["664116069"],"render_values":[{"text":"664116069","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/648","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Südhof, Thomas C."]},{"key":"dc:creator","label":"Author","values":["Gallardo, Gilbert"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07-12T18:43:53Z","2007-08-08"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text","dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["alpha-Synuclein","Neurodegenerative Diseases","Amyloid beta-Protein"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/648","664116069"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The discovery of two missense mutations (A53T and A30P) in alpha -synuclein that are genetically linked to Parkinson's disease, together with alpha -synuclein being the major component in Lewy bodies, has generated extensive interest in alpha -synuclein as a key component in neurodegenerative diseases. In recent years modeling this disease in transgenic mice and flies has lead to new understandings of alpha -synuclein function and pathogenesis in neurodegeneration. In the current study we analyzed transgenic mice overexpressing human alpha -synuclein and human alpha -synuclein mutations (A53T&A30P) to; First establish these transgenic mice as a model for degenerative diseases; second to identify potential contributing factors in neurodegeneration; third to decipher a potential function of alpha -synuclein. We first established that transgenic mice expressing human variants of alpha -synuclein developed an age dependant motor dysfunction with symptom logy characteristic of Parkinson's disease. Immunohistological studies revealed the presence of alpha -synuclein inclusions and a loss of motor neurons. Biochemical analysis identified a 4-5 fold increase in ubiquitin with altered expression of proteasomal subunits, characteristic of proteasomal impairment. In addition, we identified a significant increase in amyloid beta -peptides. Protein quantification of apolipoprotein E (ApoE) a protein that has been associated with the development of Alzheimer's disease, demonstrated a 5-15 fold increase in symptomatic transgenic mice. Ablation of ApoE in alpha -synuclein transgenic mice by genetic crosses revealed a delayed onset for motor dysfunction and an overall increase in survival. ApoE deficient transgenic mice displayed a decrease in ubiquitin and amyloid beta -peptides. This study illustrates ApoE, ubiquitin and Abeta - peptides contribute to the onset and progression of the neurodegeneration in transgenic alpha -synuclein mice. Genetic crosses of transgenic alpha -synuclein with a csystine string protein-alpha (CSPalpha ) knockout mouse revealed a potential function for alpha -synuclein. CSPalpha deficient mice develop an early age neurodegenerative disease that is lethal at 3-4 months. Transgenic expression of human alpha -synuclein prevented the deleterious effects of CSPalpha deficiency. Immunofluorescence studies illustrated alpha -synuclein function in a cell autonomous manner. Biochemical analysis demonstrated CSPalpha deficient mice have impaired SNARE complexes that are partially reverted by transgenic alpha -synuclein. This study illustrates a protective function of alpha -synuclein in preventing neurodegeneration."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital","text/plain"]},{"key":"dc:title","label":"Title","values":["An Insight into Alpha-Synulcien's Biological Function and Its Pathogenesis in Neurodegenerative Disease"]}]}],"canonical_facts":{"dc:contributor":["Südhof, Thomas C."],"dc:creator":["Gallardo, Gilbert"],"dc:date":["2010-07-12T18:43:53Z","2007-08-08"],"dc:description":["The discovery of two missense mutations (A53T and A30P) in alpha -synuclein that are genetically linked to Parkinson's disease, together with alpha -synuclein being the major component in Lewy bodies, has generated extensive interest in alpha -synuclein as a key component in neurodegenerative diseases. In recent years modeling this disease in transgenic mice and flies has lead to new understandings of alpha -synuclein function and pathogenesis in neurodegeneration. In the current study we analyzed transgenic mice overexpressing human alpha -synuclein and human alpha -synuclein mutations (A53T&A30P) to; First establish these transgenic mice as a model for degenerative diseases; second to identify potential contributing factors in neurodegeneration; third to decipher a potential function of alpha -synuclein. We first established that transgenic mice expressing human variants of alpha -synuclein developed an age dependant motor dysfunction with symptom logy characteristic of Parkinson's disease. Immunohistological studies revealed the presence of alpha -synuclein inclusions and a loss of motor neurons. Biochemical analysis identified a 4-5 fold increase in ubiquitin with altered expression of proteasomal subunits, characteristic of proteasomal impairment. In addition, we identified a significant increase in amyloid beta -peptides. Protein quantification of apolipoprotein E (ApoE) a protein that has been associated with the development of Alzheimer's disease, demonstrated a 5-15 fold increase in symptomatic transgenic mice. Ablation of ApoE in alpha -synuclein transgenic mice by genetic crosses revealed a delayed onset for motor dysfunction and an overall increase in survival. ApoE deficient transgenic mice displayed a decrease in ubiquitin and amyloid beta -peptides. This study illustrates ApoE, ubiquitin and Abeta - peptides contribute to the onset and progression of the neurodegeneration in transgenic alpha -synuclein mice. Genetic crosses of transgenic alpha -synuclein with a csystine string protein-alpha (CSPalpha ) knockout mouse revealed a potential function for alpha -synuclein. CSPalpha deficient mice develop an early age neurodegenerative disease that is lethal at 3-4 months. Transgenic expression of human alpha -synuclein prevented the deleterious effects of CSPalpha deficiency. Immunofluorescence studies illustrated alpha -synuclein function in a cell autonomous manner. Biochemical analysis demonstrated CSPalpha deficient mice have impaired SNARE complexes that are partially reverted by transgenic alpha -synuclein. This study illustrates a protective function of alpha -synuclein in preventing neurodegeneration."],"dc:format":["Electronic","application/pdf","born digital","text/plain"],"dc:identifier":["https://hdl.handle.net/2152.5/648","664116069"],"dc:language":["en"],"dc:subject":["alpha-Synuclein","Neurodegenerative Diseases","Amyloid beta-Protein"],"dc:title":["An Insight into Alpha-Synulcien's Biological Function and Its Pathogenesis in Neurodegenerative Disease"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:38Z"}