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Introduction Parkinsons disease (PD) is a chronic, progressive, and irreversible neurodegenerative disorder, first medically described by James Parkinson in 1817 (Parkinson, 2002)

Lysosomal integrity survival screen sgNT K562 dCas9-KRAB and sg NPC1 K562 dCas9-KRAB cells were infected with genome-wide sgRNA library lentivirus to target 1,000 coverage of all guides at a low MOI to ensure roughly 1 guide per cell

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After treatment, the samples were fixed with 4% paraformaldehyde, rinsed with phosphate buffer solution, and then permeabilized with 0.1% Triton-X-100

SREBP2 further enhances cholesterol production by upregulating key enzymes in the biosynthetic pathway, including 3-Hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and HMGCR [133, 185]