Figure 10

Schematic representation of disease progression in the caudate. (A) Depiction of the neuronal pathways involved in normal brain functioning, glutamatergic as well as dopaminergic innervations from cortex and substantia nigra (SN) to the caudate nucleus. (B) MPTP and PD affects the neurons in SN leading to loss of the dopaminergic projections to the caudate, leading to dysregulation of lysosomal pathways, and increasing the number of lysosomes as well as Cat D and extralysosomal Cat D. (C) Slow but persistent damage resulting from upregulation of Cat D expression and leakage leads to neuronal dysfunction and death through apoptosis or other mechanisms.