Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.
Benjamin Chun-Kit TongAston Jiaxi WuAlexis Shiying HuangRui DongSandeep MalampatiAshok IyaswamySenthilkumar KrishnamoorthiSravan Gopalkrishnashetty SreenivasmurthyZhou ZhuChengfu SuJia LiuJu-Xian SongJia-Hong LuJieqiong TanWei-Dong PanMin LiKing-Ho CheungPublished in: Autophagy (2021)
Aβ: β-amyloid; AD: Alzheimer disease; AIF1/IBA1: allograft inflammatory factor 1; ALP: autophagy-lysosomal pathway; APP: amyloid beta precursor protein; ATP6V1B1/V-ATPase V1b1: ATPase H+ transporting V1 subunit B1; AVs: autophagy vacuoles; BAF: bafilomycin A1; CFC: contextual/cued fear conditioning assay; CHX: Ca2+/H+ exchanger; CTF-β: carboxy-terminal fragment derived from β-secretase; CTSD: cathepsin D; fAD: familial Alzheimer disease; GFAP: glial fibrillary acidic protein; LAMP1: lysosomal associated membrane protein 1; LTP: long-term potentiation; MCOLN1/TRPML1: mucolipin 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPT: microtubule associated protein tau; MWM: Morris water maze; NFT: neurofibrillary tangles; PFC: prefrontal cortex; PSEN1: presenilin 1; SQSTM1/p62: sequestosome 1; TBS: theta burst stimulation; TEM: transmission electronic microscopy; TPCN2/TPC2: two pore segment channel 2; WT: wild-type; V-ATPase: vacuolar type H+-ATPase.
Keyphrases
- prefrontal cortex
- mild cognitive impairment
- wild type
- oxidative stress
- endoplasmic reticulum
- cell death
- early onset
- endoplasmic reticulum stress
- working memory
- signaling pathway
- high throughput
- protein protein
- simultaneous determination
- high resolution
- mouse model
- amino acid
- binding protein
- mass spectrometry
- small molecule
- protein kinase
- high frequency
- liquid chromatography
- high speed