Details

Autor(en) / Beteiligte

• Blandini, Fabio
• Armentero, Marie‐Therese

Titel

Animal models of Parkinson’s disease

Ist Teil von

• The FEBS journal, 2012-04, Vol.279 (7), p.1156-1166

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Animal models of Parkinson’s disease (PD) have been widely used in the past four decades to investigate the pathogenesis and pathophysiology of this neurodegenerative disorder. These models have been classically based on the systemic or local (intracerebral) administration of neutoxins that are able to replicate most of the pathological and phenotypic features of PD in mammals (i.e. rodents or primates). In the last decade, the advent of the ‘genetic era’ of PD has provided a phenomenal enrichment of the research possibilities in this field, with the development of various mammalian (mice and, more recently, rats) and non‐mammalian transgenic models that replicate most of the disease‐causing mutations identified for monogenic forms of familial PD. Both toxic and transgenic classes of animal PD models have their own specificities and limitations, which must be carefully taken into consideration when choosing the model to be used. If a substantial and reproducible nigrostriatal lesion is required (e.g. for testing therapeutic interventions aimed at counteracting PD‐related cell death), a classic toxic model such as one based on the administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine or 6‐hydroxydopamine will adequately serve the purpose. On the other hand, if selected molecular mechanisms of PD pathogenesis must be investigated, transgenic models will offer invaluable insights. Therefore, until the ‘perfect’ model is developed, indications to use one model or another will depend on the specific objectives that are being pursued. Indication to use toxic or transgenic models of Parkinson’s disease (PD) depend on the objective being pursued. When testing new therapeutic agents, a reproducible nigrostriatal lesion, as that granted by agents with selective toxicity for dopaminergic neurons, will be required. If selected molecular mechanisms must be investigated, models reproducing gene mutations associated with familial PD will offer invaluable insights