The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases.
In this work, the ability of oligomeric species of αS and Aβ to cross-propagate their oligomeric state was investigated. Oligomeric species of αS were generated in the presence of dopamine (DA) were characterized. Five discrete and stable dopamine-derived αS oligomers (DSOs) ranging from 2-14mers were fractionated. All isolated DSOs were formed along an off-fibril formation pathway. Their mechanism of formation was dependent on the oxidation of DA, implicating the quinone form of DA as an inducer of oligomerization. Importantly, DSOs could self-propagate through interactions with αS monomers. DSOs could also cross-propagate to Aβ42 monomers, yielding Aβ42 oligomers. In addition, Aβ42 oligomers (LFAOs) were shown to be capable of crosspropagating their oligomeric state to αS monomers. This work provides the first experimental evidence for the cross-propagation of oligomeric states among neurodegenerative proteins and provides a potential molecular explanation for the copathology causing increased disease severity in many PD and AD patients.
","abstract_html":"<p>The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins <strong>α</strong>-synuclein (<strong>α</strong>S) and amyloid-<strong>β </strong>(A<strong>β</strong>) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the <strong>α</strong>S and A<strong>β </strong>proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases.</p> <p>In this work, the ability of oligomeric species of <strong>α</strong>S and A<strong>β </strong>to cross-propagate their oligomeric state was investigated. Oligomeric species of <strong>α</strong>S were generated in the presence of dopamine (DA) were characterized. Five discrete and stable dopamine-derived <strong>α</strong>S oligomers (DSOs) ranging from 2-14mers were fractionated. All isolated DSOs were formed along an off-fibril formation pathway. Their mechanism of formation was dependent on the oxidation of DA, implicating the quinone form of DA as an inducer of oligomerization. Importantly, DSOs could self-propagate through interactions with <strong>α</strong>S monomers. DSOs could also cross-propagate to A<strong>β</strong>42 monomers, yielding A<strong>β</strong>42 oligomers. In addition, A<strong>β</strong>42 oligomers (LFAOs) were shown to be capable of crosspropagating their oligomeric state to <strong>α</strong>S monomers. This work provides the first experimental evidence for the cross-propagation of oligomeric states among neurodegenerative proteins and provides a potential molecular explanation for the copathology causing increased disease severity in many PD and AD patients.</p>","abstract_has_math":false,"creators":["Planchard, Matthew Stephen"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Masters Thesis","degree_discipline":"Chemistry and Biochemistry","degree_department":null,"school":null,"contributors":["Vijay Rangachari","Sabine Heinhorst","Douglas Masterson"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-05-01T07:00:00Z","date_published":"2014-05-01T07:00:00Z","updated_at":"2026-07-24T05:44:27Z","subjects":["Amyloid","synuclein","prion","propagation","oligomers","Parkinson's","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Diseases","Life Sciences","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences","Molecular and Cellular Neuroscience","Nervous System Diseases","Neuroscience and Neurobiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://aquila.usm.edu/masters_theses/25","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Vijay Rangachari","Sabine Heinhorst","Douglas Masterson"]},{"key":"dc:creator","label":"Author","values":["Planchard, Matthew Stephen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-06-08T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry and Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Amyloid","synuclein","prion","propagation","oligomers","Parkinson's","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Diseases","Life Sciences","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences","Molecular and Cellular Neuroscience","Nervous System Diseases","Neuroscience and Neurobiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://aquila.usm.edu/masters_theses/25"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases.
In this work, the ability of oligomeric species of αS and Aβ to cross-propagate their oligomeric state was investigated. Oligomeric species of αS were generated in the presence of dopamine (DA) were characterized. Five discrete and stable dopamine-derived αS oligomers (DSOs) ranging from 2-14mers were fractionated. All isolated DSOs were formed along an off-fibril formation pathway. Their mechanism of formation was dependent on the oxidation of DA, implicating the quinone form of DA as an inducer of oligomerization. Importantly, DSOs could self-propagate through interactions with αS monomers. DSOs could also cross-propagate to Aβ42 monomers, yielding Aβ42 oligomers. In addition, Aβ42 oligomers (LFAOs) were shown to be capable of crosspropagating their oligomeric state to αS monomers. This work provides the first experimental evidence for the cross-propagation of oligomeric states among neurodegenerative proteins and provides a potential molecular explanation for the copathology causing increased disease severity in many PD and AD patients.
"]},{"key":"dc:title","label":"Title","values":["Propagation of Oligomeric α-Synuclein and Amyloid-β: Implications for Parkinson's and Alzheimer's Diseases"]}]}],"canonical_facts":{"dc:contributor":["Vijay Rangachari","Sabine Heinhorst","Douglas Masterson"],"dc:creator":["Planchard, Matthew Stephen"],"dc:date.available":["2014-06-08T07:00:00Z"],"dc:description.abstract":["The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases.
In this work, the ability of oligomeric species of αS and Aβ to cross-propagate their oligomeric state was investigated. Oligomeric species of αS were generated in the presence of dopamine (DA) were characterized. Five discrete and stable dopamine-derived αS oligomers (DSOs) ranging from 2-14mers were fractionated. All isolated DSOs were formed along an off-fibril formation pathway. Their mechanism of formation was dependent on the oxidation of DA, implicating the quinone form of DA as an inducer of oligomerization. Importantly, DSOs could self-propagate through interactions with αS monomers. DSOs could also cross-propagate to Aβ42 monomers, yielding Aβ42 oligomers. In addition, Aβ42 oligomers (LFAOs) were shown to be capable of crosspropagating their oligomeric state to αS monomers. This work provides the first experimental evidence for the cross-propagation of oligomeric states among neurodegenerative proteins and provides a potential molecular explanation for the copathology causing increased disease severity in many PD and AD patients.
"],"dc:identifier":["https://aquila.usm.edu/masters_theses/25"],"dc:subject":["Amyloid","synuclein","prion","propagation","oligomers","Parkinson's","Biochemistry","Biochemistry, Biophysics, and Structural Biology","Diseases","Life Sciences","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences","Molecular and Cellular Neuroscience","Nervous System Diseases","Neuroscience and Neurobiology"],"dc:title":["Propagation of Oligomeric α-Synuclein and Amyloid-β: Implications for Parkinson's and Alzheimer's Diseases"],"thesis:degree_discipline":["Chemistry and Biochemistry"],"thesis:degree_level":["Masters Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T05:44:27Z"}