Expression of CAPON after Spinal Cord Injury in Rats

Cheng, Chun; Li, Xin; Gao, Shangfeng; Niu, Shuqiong; Chen, Meng‐Ling; Qin, Jing; Guo, Zhiqin; Zhao, Jian; Shen, Aiguo

doi:10.1007/s12031-007-9019-5

Cited by 11 publications

(9 citation statements)

References 56 publications

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“…We next examined the involvement of neuroinflammation. Shao et al 20 reported that lipopolysaccharide (LPS) stimulation induces CAPON expression, and Cheng et al 21 proposed that CAPON increases after spinal cord injury. Therefore, neuroinflammation could also be involved in the elevation of CAPON expression under amyloid pathology.…”

Section: Resultsmentioning

confidence: 99%

Tau binding protein CAPON induces tau aggregation and neurodegeneration

et al. 2019

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To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the App NL-G-F -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer’s disease (AD) pathogenesis, CAPON was overexpressed in the brain of App NL-G-F mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target.

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Section: Resultsmentioning

confidence: 99%

Tau binding protein CAPON induces tau aggregation and neurodegeneration

et al. 2019

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“…nNOS is expressed in many cell types in peripheral nervous system including Schwann cells of peripheral nerve (36), DRG neurons (37,38), and motoneurons, oligodendrocytes, and astrocytes of spinal cord (39,40). One can not exclude that it is also expressed in vasa nervorum considering recent report of the presence of nNOS in vascular endothelium (41).…”

Section: Discussionmentioning

confidence: 99%

Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency

Vareniuk

Pacher²,

Pavlov³

et al. 2009

Int J Mol Med

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Abstract. Evidence for the important role of the potent oxidant peroxynitrite in peripheral diabetic neuropathy and neuropathic pain is emerging. This study evaluated the contribution of neuronal nitric oxide synthase (nNOS) to diabetes-induced nitrosative stress in peripheral nerve and dorsal root ganglia, and peripheral nerve dysfunction and degeneration. Control and nNOS -/-mice were made diabetic with streptozotocin, and maintained for 6 weeks. Peroxynitrite injury was assessed by nitrotyrosine and poly(ADP-ribose) immunoreactivities. Peripheral diabetic neuropathy was evaluated by measurements of sciatic motor and hind-limb digital sensory nerve conduction velocities, thermal algesia, tactile allodynia, and intraepidermal nerve fiber density. Control nNOS -/-mice displayed normal motor nerve conduction velocity and thermal response latency, whereas sensory nerve conduction velocity was slightly lower compared with non-diabetic wild-type mice, and tactile response threshold and intraepidermal nerve fiber density were reduced by 47 and 38%, respectively. Both diabetic wild-type and nNOS -/-mice displayed enhanced nitrosative stress in peripheral nerve. In contrast to diabetic wild-type mice, diabetic nNOS -/-mice had near normal nitrotyrosine and poly(ADP-ribose) immunofluorescence in dorsal root ganglia. Both diabetic wild-type and nNOS -/-mice developed motor and sensory nerve conduction velocity deficits and thermal hypoalgesia although nNOS gene deficiency slightly reduced severity of the three disorders. Tactile response thresholds were similarly decreased in control and diabetic nNOS -/-mice compared with non-diabetic wild-type mice. Intraepidermal nerve fiber density was lower by 27% in diabetic nNOS -/-mice compared with the corresponding nondiabetic group, and by 20% in diabetic nNOS -/-mice compared with diabetic wild-type mice. In conclusion, nNOS is required for maintaining the normal peripheral nerve function and small sensory nerve fibre innervation. nNOS gene deficiency does not protect from development of nerve conduction deficit, sensory neuropathy and intraepidermal nerve fiber loss.

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“…16 After 1-time spinal cord injury or central nervous system infection, the expression of CAPON was increased, resulting from up-regulated expression of nNOS, thus maintaining the balance between nNOS and CAPON to prevent NO-induced neurotoxicity. 34,35 The present study showed that the expression of nNOS was increased and the expression of CAPON was decreased after ECS application once a day for 7 days, whereas the expression of nNOS was decreased and the expression of CAPON was increased after ECS application with propofol administration, implying the role of CAPON in regulating NO production by interfering with the activity of nNOS, PSD-95. Whether the expression of CAPON increased to regulate nNOS after 1-time ECS as the mechanism of compensation, or the level of CAPON would decrease after continuing ECS due to decompensation, is still a matter of debate; further investigation is necessary to confirm the fluctuation and its significance of CAPON at different time points after ECS.…”

Section: Discussionmentioning

confidence: 52%