2021
DOI: 10.3233/jpd-202221
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Treating Parkinson’s Disease with Antibodies: Previous Studies and Future Directions

Abstract: Parkinson’s disease is a neurodegenerative disorder mainly characterized by the degeneration of dopaminergic neurons in the substantia nigra. Degenerating neurons contain abnormal aggregates called Lewy bodies, that are predominantly composed of the misfolded and/or mutated alpha-synuclein protein. Post-translational modifications, cellular stress, inflammation and gene mutations are thought to trigger its pathological misfolding and aggregation. With alpha-synuclein pathology being strongly associated with do… Show more

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Cited by 34 publications
(24 citation statements)
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References 191 publications
(266 reference statements)
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“…Pathologically, the symptoms of PD are accompanied by a profound loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Dopaminergic neuron degeneration is associated with the appearance of Lewy bodies, which are predominantly composed of misfolded and/or mutated α-synuclein proteins ( 286 ). Emerging evidence supports the concept that the aberrant accumulation of misfolded and/or mutated proteins, such as α-synuclein, contributes to persistent ER stress and concomitant UPR activation, thereby resulting in dopaminergic neuronal death and degeneration, which is associated with PD ( 287 ).…”
Section: The Role Of Endoplasmic Reticulum Stress In Neurological Dis...mentioning
confidence: 99%
“…Pathologically, the symptoms of PD are accompanied by a profound loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Dopaminergic neuron degeneration is associated with the appearance of Lewy bodies, which are predominantly composed of misfolded and/or mutated α-synuclein proteins ( 286 ). Emerging evidence supports the concept that the aberrant accumulation of misfolded and/or mutated proteins, such as α-synuclein, contributes to persistent ER stress and concomitant UPR activation, thereby resulting in dopaminergic neuronal death and degeneration, which is associated with PD ( 287 ).…”
Section: The Role Of Endoplasmic Reticulum Stress In Neurological Dis...mentioning
confidence: 99%
“…The overarching goal aims to reduce the load of α-Syn pathology through a variety of means-either by targeting the process of aggregation or by targeting the consequences of aggregation. Thus far, the only clinical anti-Synuclein strategies have utilized active or passive immunization [ 23, 24 ]. Although available results to date have failed to meet the primary objective, the analysis of secondary outcome measures have signaled improvement.…”
Section: Gene Therapy Interventions Based On α-Synmentioning
confidence: 99%
“…As mentioned above, the main approach to target extracellular α-Syn, and thus cell-to-cell spread, has taken place via classic immunotherapy [ 23 ]. However, vectorized immunotherapy, in which antibodies are directly delivered to the CNS using viral vectors, is being explored in attempts to enhance target engagement within the parenchyma.…”
Section: Gene Therapy To Prevent α-Syn Pathology Propagationmentioning
confidence: 99%
“…Neuroprotection trials are again under way in these GBA mutation carrying PD patients. Currently there are also new research initiatives under way in PD with antibodies against α-synuclein based on the corresponding neuropathological findings of protein misfolding in Lewy bodies [109,110]. Various drug mechanisms aim to reduce misfolded α-synuclein and thus disease progression.…”
Section: Current Ongoing Clinical Research Strategies On Disease Modification In Pdmentioning
confidence: 99%