Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology.
Kyota FujitaHidenori HommaKanoh KondoMasashi IkunoHodaka YamakadoKazuhiko TagawaShigeo MurayamaRyosuke TakahashiHitoshi OkazawaPublished in: eNeuro (2018)
Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer's disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.
Keyphrases
- endothelial cells
- early stage
- induced pluripotent stem cells
- end stage renal disease
- pluripotent stem cells
- chronic kidney disease
- ejection fraction
- squamous cell carcinoma
- newly diagnosed
- type diabetes
- prognostic factors
- mild cognitive impairment
- protein kinase
- parkinson disease
- patient reported outcomes
- deep brain stimulation
- amino acid