Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin
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Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin. / Eggert, Simone; Thomas, Caroline; Kins, Stefan; Hermey, Guido.
In: MOL NEUROBIOL, Vol. 55, No. 7, 2018, p. 5809-5829.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin
AU - Eggert, Simone
AU - Thomas, Caroline
AU - Kins, Stefan
AU - Hermey, Guido
PY - 2018
Y1 - 2018
N2 - The amyloid precursor protein (APP), one key player in Alzheimer's disease (AD), is extensively processed by different proteases. This leads to the generation of diverging fragments including the amyloid beta (A beta) peptide, which accumulates in brains of AD patients. Subcellular trafficking of APP is an important aspect for its proteolytic conversion, since the various secretases which cleave APP are located in different cellular compartments. As a consequence, altered subcellular targeting of APP is thought to directly affect the degree to which A beta is generated. The mechanisms underlying intracellular APP transport are critical to understand AD pathogenesis and can serve as a target for future pharmacological interventions. In the recent years, a number of APP interacting proteins were identified which are implicated in sorting of APP, thereby influencing APP processing at different angles of the secretory or endocytic pathway. This review provides an update on the proteolytic processing of APP and the interplay of the transmembrane proteins low-density lipoprotein receptor-related protein 1, sortilin-receptor with A-type repeats, SorCS1c, sortilin, and calsyntenin. We discuss the specific interactions with APP, the capacity to modulate the intracellular itinerary and the proteolytic conversion of APP, a possible involvement in the clearance of A beta, and the implications of these transmembrane proteins in AD and other neurodegenerative diseases.
AB - The amyloid precursor protein (APP), one key player in Alzheimer's disease (AD), is extensively processed by different proteases. This leads to the generation of diverging fragments including the amyloid beta (A beta) peptide, which accumulates in brains of AD patients. Subcellular trafficking of APP is an important aspect for its proteolytic conversion, since the various secretases which cleave APP are located in different cellular compartments. As a consequence, altered subcellular targeting of APP is thought to directly affect the degree to which A beta is generated. The mechanisms underlying intracellular APP transport are critical to understand AD pathogenesis and can serve as a target for future pharmacological interventions. In the recent years, a number of APP interacting proteins were identified which are implicated in sorting of APP, thereby influencing APP processing at different angles of the secretory or endocytic pathway. This review provides an update on the proteolytic processing of APP and the interplay of the transmembrane proteins low-density lipoprotein receptor-related protein 1, sortilin-receptor with A-type repeats, SorCS1c, sortilin, and calsyntenin. We discuss the specific interactions with APP, the capacity to modulate the intracellular itinerary and the proteolytic conversion of APP, a possible involvement in the clearance of A beta, and the implications of these transmembrane proteins in AD and other neurodegenerative diseases.
U2 - 10.1007/s12035-017-0806-x
DO - 10.1007/s12035-017-0806-x
M3 - SCORING: Review
VL - 55
SP - 5809
EP - 5829
JO - MOL NEUROBIOL
JF - MOL NEUROBIOL
SN - 0893-7648
IS - 7
ER -
