biostudies-literatureLindberg INIA NIH HHS1463-1478https://www.ebi.ac.uk/biostudies/studies/S-EPMC9731515biostudies-literatureUnknown12(5)<h4>Background</h4>Parkinson's disease involves aberrant aggregation of the synaptic protein alpha-synuclein (aSyn) in the nigrostriatal tract. We have previously shown that proSAAS, a small neuronal chaperone, blocks aSyn-induced dopaminergic cytotoxicity in primary nigral cultures.<h4>Objective</h4>To determine if proSAAS overexpression is neuroprotective in animal models of Parkinson's disease.<h4>Methods</h4>proSAAS- or GFP-encoding lentivirus was injected together with human aSyn-expressing AAV unilaterally into the substantia nigra of rats and motor asymmetry assessed using a battery of motor performance tests. Dopamine neuron survival was assessed by nigral stereology and striatal tyrosine hydroxylase (TH) densitometry. To examine transsynaptic spread of aSyn, aSyn AAV was injected Journal of Parkinson's diseaseThe proSAAS Chaperone Provides Neuroprotection and Attenuates Transsynaptic α-Synuclein Spread in Rodent Models of Parkinson's Disease.PMC9731515R01 AG062222Helwig MMaidment NTYucer NShu ZSvendsen CNDi Monte DALindberg ILam HLaperle AfalseThe proSAAS Chaperone Provides Neuroprotection and Attenuates Transsynaptic α-Synuclein Spread in Rodent Models of Parkinson's Disease.<h4>Background</h4>Parkinson's disease involves aberrant aggregation of the synaptic protein alpha-synuclein (aSyn) in the nigrostriatal tract. We have previously shown that proSAAS, a small neuronal chaperone, blocks aSyn-induced dopaminergic cytotoxicity in primary nigral cultures.<h4>Objective</h4>To determine if proSAAS overexpression is neuroprotective in animal models of Parkinson's disease.<h4>Methods</h4>proSAAS- or GFP-encoding lentivirus was injected together with human aSyn-expressing AAV unilaterally into the substantia nigra of rats and motor asymmetry assessed using a battery of motor performance tests. Dopamine neuron survival was assessed by nigral stereology and striatal tyrosine hydroxylase (TH) densitometry. To examine transsynaptic spread of aSyn, aSyn AAV was injected 2022-01-01T00:00:00Z20222025-04-04T00:35:34.549Z2025-04-04T00:35:34.549ZS-EPMC97315153552756210.3233/jpd-21305310.3233/JPD-213053