Fig. 3.

PD and synucleinopathies as lipidopathies. Alterations in lipidostasis have been observed in several brain regions (highlighted in yellow) that are also affected by the spreading of aSyn pathology (green pathways with arrows). Given that: (i) lipids/membranes are core components of LB; (ii) that aSyn structure and lipid-binding properties are affected by the proportion of lipids in organelles; (iii) that lipidostasis alterations are linked to impaired organelle function; (iv) that neuronal lipid accumulation and high concentration of lipids in the parenchyma are associated with microglial activation and neuroinflammation; (v) that several genes involved in lipid metabolism have been identified as genetic risk factors for PD and progression; and (vi) that there is a general alteration in lipidostasis leading to accumulation of particular lipid species, we posit that these diseases should be considered not only proteinopathies but also lipidopathies