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Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification.

Wolfe DM, Lee JH, Kumar A, Lee S, Orenstein SJ, Nixon RA.

Eur J Neurosci. 2013 Jun;37(12):1949-61. doi: 10.1111/ejn.12169.


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

Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA.

Cell. 2010 Jun 25;141(7):1146-58. doi: 10.1016/j.cell.2010.05.008. Epub 2010 Jun 10.


Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime.

McBrayer M, Nixon RA.

Biochem Soc Trans. 2013 Dec;41(6):1495-502. doi: 10.1042/BST20130201. Review.


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

Lee JH, McBrayer MK, Wolfe DM, Haslett LJ, Kumar A, Sato Y, Lie PP, Mohan P, Coffey EE, Kompella U, Mitchell CH, Lloyd-Evans E, Nixon RA.

Cell Rep. 2015 Sep 1;12(9):1430-44. doi: 10.1016/j.celrep.2015.07.050. Epub 2015 Aug 20.


Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer's disease-linked presenilin 1 A246E mutation can be reversed with cAMP.

Coffey EE, Beckel JM, Laties AM, Mitchell CH.

Neuroscience. 2014 Mar 28;263:111-24. doi: 10.1016/j.neuroscience.2014.01.001. Epub 2014 Jan 10.


Autophagy failure in Alzheimer's disease--locating the primary defect.

Nixon RA, Yang DS.

Neurobiol Dis. 2011 Jul;43(1):38-45. doi: 10.1016/j.nbd.2011.01.021. Epub 2011 Feb 3. Review.


Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits.

Yang DS, Stavrides P, Saito M, Kumar A, Rodriguez-Navarro JA, Pawlik M, Huo C, Walkley SU, Saito M, Cuervo AM, Nixon RA.

Brain. 2014 Dec;137(Pt 12):3300-18. doi: 10.1093/brain/awu278. Epub 2014 Sep 29.


Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer's disease.

Lee JK, Jin HK, Park MH, Kim BR, Lee PH, Nakauchi H, Carter JE, He X, Schuchman EH, Bae JS.

J Exp Med. 2014 Jul 28;211(8):1551-70. doi: 10.1084/jem.20132451. Epub 2014 Jul 21.


Approaches for detecting lysosomal alkalinization and impaired degradation in fresh and cultured RPE cells: evidence for a role in retinal degenerations.

Guha S, Coffey EE, Lu W, Lim JC, Beckel JM, Laties AM, Boesze-Battaglia K, Mitchell CH.

Exp Eye Res. 2014 Sep;126:68-76. doi: 10.1016/j.exer.2014.05.013. Review.


Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits.

Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA.

Brain. 2011 Jan;134(Pt 1):258-77. doi: 10.1093/brain/awq341.


Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy.

Joshi G, Gan KA, Johnson DA, Johnson JA.

Neurobiol Aging. 2015 Feb;36(2):664-79. doi: 10.1016/j.neurobiolaging.2014.09.004. Epub 2014 Sep 6.


Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis.

Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson DW, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA.

Autophagy. 2011 Jul;7(7):788-9. Epub 2011 Jul 1.


A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2.

Zhang X, Garbett K, Veeraraghavalu K, Wilburn B, Gilmore R, Mirnics K, Sisodia SS.

J Neurosci. 2012 Jun 20;32(25):8633-48. doi: 10.1523/JNEUROSCI.0556-12.2012.


Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a γ-secretase-independent manner.

Neely KM, Green KN, LaFerla FM.

J Neurosci. 2011 Feb 23;31(8):2781-91. doi: 10.1523/JNEUROSCI.5156-10.2010.


The autophagy-lysosomal degradation pathway: role in neurodegenerative disease and therapy.

Shacka JJ, Roth KA, Zhang J.

Front Biosci. 2008 Jan 1;13:718-36. Review.


Macroautophagy is not directly involved in the metabolism of amyloid precursor protein.

Boland B, Smith DA, Mooney D, Jung SS, Walsh DM, Platt FM.

J Biol Chem. 2010 Nov 26;285(48):37415-26. doi: 10.1074/jbc.M110.186411. Epub 2010 Sep 23.


Presenilin 1 regulates epidermal growth factor receptor turnover and signaling in the endosomal-lysosomal pathway.

Repetto E, Yoon IS, Zheng H, Kang DE.

J Biol Chem. 2007 Oct 26;282(43):31504-16. Epub 2007 Aug 23.


Altered levels and distribution of IGF-II/M6P receptor and lysosomal enzymes in mutant APP and APP + PS1 transgenic mouse brains.

Amritraj A, Hawkes C, Phinney AL, Mount HT, Scott CD, Westaway D, Kar S.

Neurobiol Aging. 2009 Jan;30(1):54-70. Epub 2007 Jun 11.


A neuronal model of Alzheimer's disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury.

Sompol P, Ittarat W, Tangpong J, Chen Y, Doubinskaia I, Batinic-Haberle I, Abdul HM, Butterfield DA, St Clair DK.

Neuroscience. 2008 Apr 22;153(1):120-30. doi: 10.1016/j.neuroscience.2008.01.044. Epub 2008 Feb 7.

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