Defective autophagy and Alzheimer's disease: is calcium the key?
|
摘要
<正>Presenilins and autophagy:Presenilin 1 (PS1) and presenilin 2 (PS2)arehomologous,multi-passtransmembraneproteinsendowedwith pleiotropic functions, ranging from the regulation of membrane trafficking to cell differentiation. Their catalytic activity within theγ-secretase complex, an aspartyl-protease responsible for the intramembrane cleavage of several different type I transmembrane proteins, has been intensively studied in the context of Alzheimer’s disease (AD). Indeed,
引文
Coen K,Flannagan RS,Baron S,Carraro-Lacroix LR,Wang D,Vermeire W,Michiels C,Munck S,Baert V,Sugita S,Wuytack F,Hiesinger PR,Grinstein S,Annaert W(2012)Lysosomal calcium homeostasis defects,not proton pump defects,cause endo-lysosomal dysfunction in PSEN-deficient cells.J Cell Biol 198:23-35.
Fedeli C,Filadi R,Rossi A,Mammucari C,Pizzo P(2019)PSEN2(presenilin 2)mutants linked to familial Alzheimer disease impair autophagy by altering Ca(2+)homeostasis.Autophagy doi:10.1080/15548627.2019.1596489.
Greotti E,Capitanio P,Wong A,Pozzan T,Pizzo P,Pendin D(2019)Familial Alzheimer’s disease-linked presenilin mutants and intracellular Ca2+handling:A single-organelle,FRET-based analysis.Cell Calcium 279:44-56.
Gutierrez MG,Munafo DB,Beron W,Colombo MI(2004)Rab7 is required for the normal progression of the autophagic pathway in mammalian cells.J Cell Sci 117:2687-2697.
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(2015)Presenilin 1 maintains lysosomal Ca2+homeostasis via TRP-ML1 by regulating vATPase-mediated lysosome acidification.Cell Rep12:1430-1444.
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(2010)Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.Cell 141:1146-1158.
Medina DL,Di Paola S,Peluso I,Armani A,De Stefani D,Venditti R,Montefusco S,Scotto-Rosato A,Prezioso C,Forrester A,Settembre C,Wang W,Gao Q,Xu H,Sandri M,Rizzuto R,De Matteis MA,Ballabio A(2015)Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.Nat Cell Biol 17:288-299.
Neely KM,Green KN,LaFerla FM(2011)Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a gamma-secretase-independent manner.J Neurosci 31:2781-2791.
Reddy K,Cusack CL,Nnah IC,Khayati K,Saqcena C,Huynh TB,Noggle SA,Ballabio A,Dobrowolski R(2016)Dysregulation of nutrient sensing and CLEARance in presenilin deficiency.Cell Rep 14:2166-2179.
Sannerud R,Esselens C,Ejsmont P,Mattera R,Rochin L,Tharkeshwar AK,De Baets G,De Wever V,Habets R,Baert V,Vermeire W,Michels C,Groot AJ,Wouters R,Dillen K,Vints K,Baatsen P,Munck S,Derua R,Waelkens E,et al.(2016)Restricted location of PSEN2/γ-secretase determines substrate specificity and generates an intracellular Aβpool.Cell166:1-16.
Wilson CA,Murphy DD,Giasson BI,Zhang B,Trojanowski JQ,Lee VM(2004)Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons.J Cell Biol 165:335-346.
Zhang X,Garbett K,Veeraraghavalu K,Wilburn B,Gilmore R,Mirnics K,Sisodia SS(2012)A role for presenilins in autophagy revisited:normal acidification of lysosomes in cells lacking PSEN1 and PSEN2.J Neurosci32:8633-8648.
Fedeli C,Filadi R,Rossi A,Mammucari C,Pizzo P(2019)PSEN2(presenilin 2)mutants linked to familial Alzheimer disease impair autophagy by altering Ca(2+)homeostasis.Autophagy doi:10.1080/15548627.2019.1596489.
Greotti E,Capitanio P,Wong A,Pozzan T,Pizzo P,Pendin D(2019)Familial Alzheimer’s disease-linked presenilin mutants and intracellular Ca2+handling:A single-organelle,FRET-based analysis.Cell Calcium 279:44-56.
Gutierrez MG,Munafo DB,Beron W,Colombo MI(2004)Rab7 is required for the normal progression of the autophagic pathway in mammalian cells.J Cell Sci 117:2687-2697.
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(2015)Presenilin 1 maintains lysosomal Ca2+homeostasis via TRP-ML1 by regulating vATPase-mediated lysosome acidification.Cell Rep12:1430-1444.
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(2010)Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.Cell 141:1146-1158.
Medina DL,Di Paola S,Peluso I,Armani A,De Stefani D,Venditti R,Montefusco S,Scotto-Rosato A,Prezioso C,Forrester A,Settembre C,Wang W,Gao Q,Xu H,Sandri M,Rizzuto R,De Matteis MA,Ballabio A(2015)Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.Nat Cell Biol 17:288-299.
Neely KM,Green KN,LaFerla FM(2011)Presenilin is necessary for efficient proteolysis through the autophagy-lysosome system in a gamma-secretase-independent manner.J Neurosci 31:2781-2791.
Reddy K,Cusack CL,Nnah IC,Khayati K,Saqcena C,Huynh TB,Noggle SA,Ballabio A,Dobrowolski R(2016)Dysregulation of nutrient sensing and CLEARance in presenilin deficiency.Cell Rep 14:2166-2179.
Sannerud R,Esselens C,Ejsmont P,Mattera R,Rochin L,Tharkeshwar AK,De Baets G,De Wever V,Habets R,Baert V,Vermeire W,Michels C,Groot AJ,Wouters R,Dillen K,Vints K,Baatsen P,Munck S,Derua R,Waelkens E,et al.(2016)Restricted location of PSEN2/γ-secretase determines substrate specificity and generates an intracellular Aβpool.Cell166:1-16.
Wilson CA,Murphy DD,Giasson BI,Zhang B,Trojanowski JQ,Lee VM(2004)Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons.J Cell Biol 165:335-346.
Zhang X,Garbett K,Veeraraghavalu K,Wilburn B,Gilmore R,Mirnics K,Sisodia SS(2012)A role for presenilins in autophagy revisited:normal acidification of lysosomes in cells lacking PSEN1 and PSEN2.J Neurosci32:8633-8648.