Table 7 Alfa-synuclein immunization studies in animal models of PD Tg-trangenic, hSNCA-human alfa synuclein, rh-SNCA-recombinant human alfa synuclein, rAAV-recombinant adeno-associated virus, SN-substantia niagara, PDGF-platelet derived growth factor, TH-tyrosine hydroxylase, Ag-antigen, Ab-antibody, APOE-Apolipoprotein E

Animal models

Ag/Ab

Outcomes

 Tg-mice expressing hSNCA under the PDGF-β promoter, D-line

rh-SNCA

Reduction of accumulated SNCA in neurons and higher number of synaptophysin-positive nerve terminals ameliorating neuronal damage, mild microglia activation

[29, 179, 180]

 Sprague-Dawley rats injected with rAAV-SNCA into SN

rh-SNCA

Reduction of SNCA inclusions in SN, induction of regulated T cells and activated microglia

[180, 339]

 Two models: PDGF-SNCA mice expressing hSNCA under the PDGF-β promoter and mThy1-SNCA mice expressing hSNCA under the murine Thy1 promoter

C-terminus of SNCA (aa 110–130), also able to bind to full-length and N-terminal-truncated forms of α- syn, such as SNCA 96–140

Reduced SNCA oligomers in axons and synapses, reduced degeneration of striatal TH-immunoreactive fibers, clearance of SNCA involved microglia, improved motor and cognitive deficits in both models

[180, 340]

 Mice expressing hSNCA under the control of the myelin basic protein promoter

Ag mimicking the C-terminus of SNCA or the original C-terminus peptide (aa 110–130)

Decreased accumulation of SNCA, reduced demyelination in neocortex, striatum and corpus callosum, reduced neurodegeneration, activation and clearance of SNCA by microglia, reduced spreading of SNCA to astrocytes

[341]

 Tg-mice expressing hSNCA under the PDGF-β promoter, D-line

SNCA C-terminus Ab-9E4 (IgG1), epitope 118–126

Reduction of calpain-cleaved SNCA in neurons, no difference in microglia activation between control and Ab-treated mice, less motor and cognitive impairment

[342]

 Tg-mice expressing hSNCA under the PDGF-β promoter, M-line

SNCA C-terminus Ab274 (IgG2a), epitope 120–140

Reduced accumulation of SNCA in neurons and astroglia, increased presence of SNCA in microglia, improved function in open field and pole tests

[180]

 Tg-mice expressing hSNCA under the Thy-1 promoter, line 61

C-Terminus SNCA Ab: 1H7, 9E4, 5C1, and 5D12

Attenuated synaptic and axonal pathology in cortex, hippocampus and striatum, reduced accumulation of C-terminus-truncated SNCA in striatal axons and mitigated loss of TH fibers, reduced astrogliosis and microgliosis, improved motor and cognitive deficits

[343]

 Tg-mice expressing hA30P SNCA under the Thy-1 promoter

SNCA protofibril-selective monoclonal Ab (mAb47)

Reductions of soluble and membrane-associated SNCA protofibrils in spinal cord, no change of astrocytic or microglial activity

 Mice overexpressing hSNCA under the PDGF-β promoter (line D)

Single-chain fragment variables against oligomeric SNCA fused to the low-density lipoprotein receptor-binding domain of APOE-B

Decreased oligomeric and phosphorylated SNCA accumulation in neocortex and hippocampus, reduced levels of astrocytes, improved memory function

[344]

 Intrastriatal stereotaxic injections of SNCA preformed fibrils in wild type C57Bl6/C3H-mice

Monoclonal Ab: Syn303 (binds pathological conformations of human and mouse SNCA) targeting N-terminus)

Reduction of LB, amelioration of nigral DA-neuron loss, no differences in astrogliosis and microgliosis, improved motor behavior

[345]

 Fisher 344 male rats injected into SN with rAAV expressing hSNCA

Ab against the N-terminal or central region of SNCA

Lowered levels of SNCA, reduced SNCA-induced DA-neuron loss, decreased number of activated microglia, partial improvement of behavioral deficits

[346]