Direct MRI-guided stereotaxic viral mediated gene transfer of alpha-synuclein in the Göttingen minipig CNS.

The aim was to establish a non-primate large animal PD model by lentiviral vector mediated mutant alpha-synuclein overexpression in the substantia nigra. Lentivirus encoding A53T alpha-synuclein (6 x 2.5 μl) was stereotaxically injected into the substantia nigra of six adult female Göttingen minipigs.

Direct gene transfer in the Gottingen minipig CNS using stereotaxic lentiviral microinjections.

We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Gottingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Gottingen minipigs were injected unilaterally into the SN with 6 per 2.5 microliters lentivirus capable of transducing cells and mediating expression of recombinant EGFP.

Threonine 53 in alpha-synuclein is conserved in long-living non-primate animals.

Alpha-synuclein is the main constituent of Lewy bodies in familial and sporadic cases of Parkinson's disease (PD). Autosomal dominant point mutations, gene duplications or triplications in the alpha-synuclein (SNCA) gene cause hereditary forms of PD. One of the alpha-synuclein point mutations, Ala53Thr, is associated with increased oligomerization toxicity leading to familial early-onset PD in humans.

Identification of multiple post-translational modifications in the porcine brain specific p25alpha.

P25alpha is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25alpha occurs in multiple system atrophy, Parkinson's disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated alpha-synuclein and is a potent stimulator of alpha-synuclein aggregation. P25alpha is a phosphoprotein and post-translational modifications (PTMs) may play a role in its disease-related abnormalities.