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Deciphering Alzheimer's: TRPC1 as a central player in protein unfolding and cholesterol biosynthesis
- Abstract
- Background: Alzheimer’s disease (AD) is an irreversible and fatal form of dementia, divided into sporadic (SAD) and familial AD (FAD). FAD, with early onset due to specific gene mutations, contrasts SAD, with late onset and an unclear cause. The Ca2+ homeostasis hypothesis of SAD suggests early Ca2+ dyshomeostasis links to protein misfolding and cholesterol accumulation. The endoplasmic reticulum (ER) is crucial, managing intracellular Ca2+, protein processing, and lipid biosynthesis. The transient receptor potential canonical family (TRPC1-7) includes TRPC1, highly expressed in the hippocampus. While TRPC2-7 target the plasma membrane, TRPC1 is also found in the ER membrane.
Hypothesis: TRPC1 may be involved in Ca2+ handling, protein, and cholesterol synthesis in the ER.
Results: Preliminary experiments showed TRPC1 increased Ca2+ leak from the ER, elevated cholesterol in TRPC1- transfected HEK293 cells, altered cholesterol levels in hippocampi from aged transgenic mice, and affected expression of transcription factors involved in protein folding.
Conclusion: Further exploring TRPC1 role in the ER could establish it as a potential pharmaceutical target in AD treatment.
- Keywords
- Alzheimer-Krankheit
- Ca2+-Homöostase
- Hippocampus
- Proteinen und Lipid-Biosynthese
- TRPC1
- Project Leader:
- Tiapko Oleksandra
- Duration:
- 01.03.2024-31.03.2026
- Type of Research
- applied research
- MUG Research Units
- Division of Medical Physics and Biophysics