Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult rat.
Regulated intramembrane proteolysis (RIP) is one of the signaling pathways mediating information transfer from the extracellular to the intracellular domain. gamma-Secretase is an aspartyl protease of the RIP that cleaves the intramembrane region of type I integral membrane proteins, such as amyloid precursor protein (APP). Presenilin 1 (PS1) is the catalytic subunit of gamma-secretase and PS1 mutations cause Alzheimer's disease, spastic paraplegia and spinal cord atrophy. The biological function of PS1 in the spinal cord has not been fully elucidated. Thus, to clarify the involvement of RIP in spinal cord injury, we examined the expression of PS1, APP and amyloid-beta protein (Abeta) following rat spinal cord hemisection. Western blot analysis showed that PS1, APP and Abeta levels increased 1 day after spinal cord hemisection. Immunohistochemistry showed an increased number of PS1 immunopositive cells about 1mm from the lesion site. PS1, APP and Abeta double staining with cell-type specific markers showed colocalization of PS1 with axons in the white matter of the lesioned side. These findings suggest that RIP signaling occurs following rat spinal cord injury. In the future, the control of RIP may offer a new strategy for the treatment of spinal cord injury.
Kobayashi
S
S
Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
Sasaki
T
T
Katayama
T
T
Hasegawa
T
T
Nagano
A
A
Sato
K
K
D000208:Acute Disease; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D020134:Catalytic Domain / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010447:Peptide Hydrolases