Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.

Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.

Autophagy (2021-07-28)

Benjamin Chun-Kit Tong, Aston Jiaxi Wu, Alexis Shiying Huang, Rui Dong, Sandeep Malampati, Ashok Iyaswamy, Senthilkumar Krishnamoorthi, Sravan Gopalkrishnashetty Sreenivasmurthy, Zhou Zhu, Chengfu Su, Jia Liu, Juxian Song, Jia-Hong Lu, Jieqiong Tan, Weidong Pan, Min Li, King-Ho Cheung

PMID34313551

ABSTRACT

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.

MATERIALS

Product Number

Brand

Product Description

P0067

Sigma-Aldrich

Anti-p62/SQSTM1 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution

MAB1501R

Sigma-Aldrich

Anti-Actin Antibody, clone C4, clone C4, Chemicon^®, from mouse

MAB5232

Sigma-Aldrich

Anti-Presenilin-1 Antibody, loop, a.a. 263-378, CT, clone PS1-loop, ascites fluid, clone PS1-loop, Chemicon^®