Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1−/− mice

Parkinson’s disease is characterized by massive motor impairment which is caused by the progressive degeneration of dopaminergic neurons of the substantia nigra (SN) in the mesencephalon.

Heritable, rare forms (less than 10%) of this pathology are characterized by impaired mitochondrial fuction, which seems to be linked to a mutation in PINK1, a gene encoding for a protein that elicits some sort of quality control over mitochondria, by “enlisting” them for degradation when they are damaged and dysfunctional. Impairment of PINK1 leads to accumulation of damaged mitochondria. However, Matheoud et al. proposed that PINK1 impairment also leads to an autoimmune outcome which might be relevant for PD.
Indeed, PINK1-ko mice exposed to bacteria display a parkinsonian phenotype which can be reverted by L-DOPA treatment, a drug used in PD treatment. The proposed mechanism involves dendritic cells of ko mice that, under bacterial infection, display membrane MHC proteins loaded with mitochondrial autoantigens, which might derive from mitochondrial engulfment resulting from PINK1 loss of function.

This way, dendritic cells would instruct adaptive cell-mediated immunity to convey an autoimmune attack towards dopaminergic SN neurons. Indeed, not only infected PINK1-ko  mice feature dendritic cells displaying mitochondrial autoantigens, but also, culturing their T cells in presence of these peptides leads to the generation of CTL that target primary neurons from PINK1-ko.

Source: Nature (synopsis)
Original paper

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