Objective: We aim to validate the neuroprotective potential of SLP-2 against α-syn neuropathology and neurodegeneration of dopaminergic neurons in a mouse model of Parkinson’s disease.
Background: One of the main histologic hallmarks in Parkinson’s disease (PD) is the apparition of abnormal protein aggregates, mainly composed of α-synuclein (α-syn) known as Lewy bodies. These structures are involved in toxic processes leading to mitochondrial dysfunction and increase the vulnerability of dopaminergic neurons to degeneration. There is still no cure for PD so the development of neuroprotective therapies is needed. Stomatin-like protein 2 (SLP-2) is a protein located in the inner mitochondrial membrane and acts as a membrane scaffold regulating mitochondrial function, integrity and bioenergetic. Previous results from our team showed that SLP-2 protein expression is reduced in dopaminergic neurons of human PD post-mortem brains. Our hypothesis is that SLP-2 overexpression in the dopaminergic neurons of the substantia nigra pars compacta (SNpc) will confer protection against α-syn toxicity.
Method: We used viral-vector-based delivery of AAV virus containing human mutated A53T α-syn and we simultaneously overexpressed SLP-2 in the SNpc by stereotaxic injections. Mitochondrial oxygen respiration was studied by high-resolution respirometry (OROBOROS). Dopaminergic cell survival in the SNpc was quantified by stereology using TH and NeuN markers.
Results: Upon induction of α-syn expression in SNpc, we measured a significant decrease in mitochondrial oxygen respiration that could be rescued by SLP-2 forced expression, indicating that SLP-2 is able to mitigate α-syn toxicity. The histologic analysis also revealed that SLP-2 could protect dopamine neurons in the SNpc against α-syn toxicity.
Conclusion: Our preliminary results indicate that SLP-2 overexpression can protect dopaminergic neurons against α-syn toxicity and neurodegeneration. SLP-2 could thus represent a novel therapeutic target to treat or to prevent Parkinson’s disease.
To cite this abstract in AMA style:
C. Bolduc, M. Lorente Picón, S. Laouafa, J. Soliz, I. Pichler, M. Lévesque. Validation of the Neuroprotective Potential of SLP-2 against alpha-synuclein neuropathology in a Mouse Model of Parkinson’s Disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/validation-of-the-neuroprotective-potential-of-slp-2-against-alpha-synuclein-neuropathology-in-a-mouse-model-of-parkinsons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/validation-of-the-neuroprotective-potential-of-slp-2-against-alpha-synuclein-neuropathology-in-a-mouse-model-of-parkinsons-disease/