Pilot Study Sheds New Light on Neurodegenerative Diseases
A new study has brought to light insights into the mechanisms underlying neurodegenerative diseases, particularly synucleinopathies like Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Conducted by a consortium of researchers from the University of Bordeaux (France), the University of San Pablo Madrid, the University of Barcelona and Murcia, this study demonstrates the toxicity of patient-derived extracts, their potential to propagate through the brain, and offers a novel primate model for DLB.
Aggregation of α-synuclein (α-syn) proteins is a pivotal factor in synucleinopathies, affecting both humans and non-human primates. This study focused on understanding the progression of α-syn pathology. It revealed that mesencephalic Lewy bodies (LB) injections in non-human primates resulted in widespread prefrontal neuronal loss, prefrontal inflammation, and pSyn immunoreactivity one year after intracortical administration. This prefrontal cortex pathology was accompanied by pSyn accumulation in the caudate nucleus but not in the putamen, indicating a unique pattern of pathology and striatal dopaminergic function alteration. The study also highlighted the propagation of α-syn pathology from the cortex to the striatum in non-human primates, mirroring aspects of DLB.
One of the lead researchers, Dr. Dehay noted that, “While this proof-of-concept pilot study is encouraging, pending questions await future investigation in more animals. One aspect should include the injection of cortical LB fractions to observe the varying cellular vulnerability and the potential for more pronounced pathological effects while keeping animals longer. These findings could lead to a better understanding of α-synuclein propagation and toxicity in a species close to humans and the role of the prefrontal cortex in LB pathology.”
Overall, the study’s findings emphasise the importance of non-human primates as a crucial testbed for understanding synucleinopathies due to their similarities in brain anatomy and human function. The research paves the way for a deeper understanding of the mechanisms underlying α-synuclein-induced cell death, intending to identify biomarkers for enhanced patient diagnosis and therapeutic interventions during the earliest stages of these devastating diseases.
The teams of Drs Bezard & Dehay, Obeso, Vila and Herrero remain committed to advancing knowledge in the field of neurodegenerative diseases, and this pilot study represents a significant step towards unlocking the mysteries of synucleinopathies.
Reference
Teil M, Dovero S, Bourdenx M, Arotcarena ML, Darricau M, Porras G, Thiolat ML, Trigo-Damas I, Perier C, Estrada C, Garcia-Carrillo N, Herrero MT, Vila M, Obeso JA, Bezard E#, Dehay B#. (2023)
Cortical Lewy body injections induce long-distance pathogenic alterations in the non-human primate brain.
NPJ Parkinsons Dis. 2023 Sep 19;9(1):135.
doi: 10.1038/s41531-023-00579-w
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Last update 23/10/23