Age-related intraneuronal accumulation of αII-spectrin breakdown product SBDP120 in the human cerebrum is enhanced in Alzheimer's disease.
Exp Gerontol
; 69: 43-52, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26051930
ABSTRACT
Spectrins are a part of cytoskeletal platform that lines the intracellular side of plasma membrane, which can be proteolyzed by calcium-sensitive enzymes including calpains and caspases. Caspase-3 mediated αII-spectrin proteolysis results in the release of a 120kDa spectrin breakdown product (SBDP120), known to occur in conditions with cell death. In rodents, intraneuronal SBDP120 accumulation in the forebrain develops with age, which is enhanced in transgenic models of Alzheimer's disease (AD). The present study was set to explore age-related SBDP120 formation and its relevance to AD-type hallmark lesions in the human brains. SBDP120 immunoreactivity (IR) was detected in neuronal somata and dendrites in the cortex and hippocampal formation in postmortem brains from aged (n=10, mean age=84.2) and AD (n=10, mean age=84.8) subjects, but not mid-aged controls (n=10, mean age=58.2). The overall density of SBDP120 IR quantified in the temporal neocortex was increased in the aged and AD groups, more robust in the latter, relative to mid-aged control, while no regional, laminar or cellular association was found between SBDP120 accumulation and Aß deposition or phosphorylated-tau aggregation. In cultured rat retinal ganglion cells (RGC-5), SBDP120 elevation occurred with caspase-3 activation following oxygen as well as serum deprivation, suggestive of SBDP120 formation in stressful conditions with and without apparent neuronal death. These results confirm an age-related intraneuronal SBDP120 accumulation in the human cerebrum that is enhanced in AD. This neuronal change appears to occur independent of amyloid deposition, tau pathology and overt neuronal death.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
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Proteínas tau
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Proteínas de Transporte Vesicular
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Enfermedad de Alzheimer
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Proteínas de Microfilamentos
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Neuronas
Límite:
Aged
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Aged80
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Animals
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Humans
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Middle aged
Idioma:
En
Revista:
Exp Gerontol
Año:
2015
Tipo del documento:
Article
País de afiliación:
China