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Literature DB >> 34313551

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

Benjamin Chun-Kit Tong¹, Aston Jiaxi Wu¹, Alexis Shiying Huang¹, Rui Dong², Sandeep Malampati¹, Ashok Iyaswamy¹, Senthilkumar Krishnamoorthi¹, Sravan Gopalkrishnashetty Sreenivasmurthy¹, Zhou Zhu¹, Chengfu Su¹, Jia Liu¹, Juxian Song³, Jia-Hong Lu⁴, Jieqiong Tan⁵, Weidong Pan⁶, Min Li¹, King-Ho Cheung¹.

Abstract

ABBREVIATIONS: 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.

Entities: Chemical

Keywords: Alzheimer disease; autophagy-lysosomal pathway; calcium ion; presenilin-1; two pore segment channel 2

Mesh：

Substances：

Year: 2021 PMID： 34313551 PMCID： PMC9037479 DOI： 10.1080/15548627.2021.1945220

Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 13.391

59 in total

1. Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.

Authors: Ju-Hyun Lee; Mary Kate McBrayer; Devin M Wolfe; Luke J Haslett; Asok Kumar; Yutaka Sato; Pearl P Y Lie; Panaiyur Mohan; Erin E Coffey; Uday Kompella; Claire H Mitchell; Emyr Lloyd-Evans; Ralph A Nixon
Journal: Cell Rep Date: 2015-08-20 Impact factor: 9.423

2. Monitoring autophagy in Alzheimer's disease and related neurodegenerative diseases.

Authors: Dun-Sheng Yang; Ju-Hyun Lee; Ralph A Nixon
Journal: Methods Enzymol Date: 2009 Impact factor: 1.600

3. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

Authors: Ju-Hyun Lee; W Haung Yu; Asok Kumar; Sooyeon Lee; Panaiyur S Mohan; Corrinne M Peterhoff; Devin M Wolfe; Marta Martinez-Vicente; Ashish C Massey; Guy Sovak; Yasuo Uchiyama; David Westaway; Ana Maria Cuervo; Ralph A Nixon
Journal: Cell Date: 2010-06-10 Impact factor: 41.582

4. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice.

Authors: Fiona Pickford; Eliezer Masliah; Markus Britschgi; Kurt Lucin; Ramya Narasimhan; Philipp A Jaeger; Scott Small; Brian Spencer; Edward Rockenstein; Beth Levine; Tony Wyss-Coray
Journal: J Clin Invest Date: 2008-06 Impact factor: 14.808

Review 5. The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels.

Authors: Antony Galione; A Mark Evans; Jianjie Ma; John Parrington; Abdelilah Arredouani; Xiaotong Cheng; Michael X Zhu
Journal: Pflugers Arch Date: 2009-05-28 Impact factor: 3.657

6. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production.

Authors: Kim N Green; Angelo Demuro; Yama Akbari; Brian D Hitt; Ian F Smith; Ian Parker; Frank M LaFerla
Journal: J Cell Biol Date: 2008-06-30 Impact factor: 10.539

7. TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.

Authors: Margarida Ruas; Kai-Ting Chuang; Lianne C Davis; Areej Al-Douri; Patricia W Tynan; Ruth Tunn; Lydia Teboul; Antony Galione; John Parrington
Journal: Mol Cell Biol Date: 2014-08-18 Impact factor: 4.272

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

1. Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.

2. Monitoring autophagy in Alzheimer's disease and related neurodegenerative diseases.

3. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

4. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice.

Review 5. The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels.

6. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production.

7. TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.

8. Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency.

9. Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons.

10. Golgi-Cox Staining Step by Step.

Review 1. Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis.

2. Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model.

3. Two-pore channels: going with the flows.

Review 4. Targeting the two-pore channel 2 in cancer progression and metastasis.

Review 5. Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer's Disease: A Review.