LRRK2 and proteostasis deficiencies: A proposed mechanism by which PSEN1 I146T induces proteinopathy, OS, and apoptosis in DALNs is shown in Figure 14A. Interestingly, the LRRK2 kinase inhibitor PF-475 reverses the PSEN1 I146T-induced mixed pathology markers in DALNs (Figure 14B).