Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases

Álvarez, Jaime; Moreno, Ricardo D.; Llanos, O; Inestrosa, Nibaldo C.; Brandan, Enrique; Colby, Tim; Esch, Frederick

doi:10.1016/0304-3940(92)90733-n

Cited by 58 publications

(29 citation statements)

References 28 publications

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“…3). The protection exerted by APP 135-156 is in agreement with previous studies demonstrating neuroprotective and neurotrophic activities for soluble APP (8,9).…”

Section: App and Its Role In Copper Homeostasissupporting

confidence: 80%

Copper brain homeostasis: Role of amyloid precursor protein and prion protein

Inestrosa

Cerpa

Varela-Nallar

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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The main proteins associated with Alzheimer's and prion diseases (amyloid precursor protein (APP) and prion protein (PrPC), respectively, have binding sites for copper and it has therefore been suggested that they play a role in copper metabolism. Here, we review evidence indicating that the copper binding domains (CuBD) of APP and PrPC are able to modulate the oxidation state of copper, and prevent neurotoxic effects and memory impairments induced by copper. Results with transgenic and other animal models have established the relation between these pathogenic proteins and copper. In particular, APP transgenic models, suggest a beneficial effect for copper in AD. IUBMB Life, 57: 645‐650, 2005

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“…3). The protection exerted by APP 135-156 is in agreement with previous studies demonstrating neuroprotective and neurotrophic activities for soluble APP (8,9).…”

Section: App and Its Role In Copper Homeostasissupporting

confidence: 80%

Copper brain homeostasis: Role of amyloid precursor protein and prion protein

Inestrosa

Cerpa

Varela-Nallar

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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“…The latter may be attributable to sprouting of the regenerating nerve fibers. 1,29,62 There was a wide distribution of area measurements among the 4-week groups. Interestingly, the axonal area measured at the proximal level in the tube + SCs group was almost twice as large as the area measured at the midpoint level.…”

Section: Histological Analysis Of Regenerated Cables Within Treatmentmentioning

confidence: 99%

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

Berrocal

Almeida

Gupta

et al. 2013

JNS

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Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

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“…APP is also expressed in the peripheral nervous system (PNS). 14 However, in contrast to APP's nodal location in the CNS, APP immunoreactivity was evenly distributed along myelinated fibers in the adult rat sciatic nerve. This was shown by double immunofluorescence labeling with APP and juxtaparanodal potassium channels Kv1.2 (Fig.…”

Section: App Clusters At Nors In the Cns But Not Pnsmentioning

confidence: 92%

Amyloid precursor protein at node of Ranvier modulates nodal formation

Zhang

Yang

et al. 2014

Cell Adhesion & Migration

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These authors contributed equally to this work.Keywords: APP, sodium channels, nodes of Ranvier, paranode, myelination Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.

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Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases

Cited by 58 publications

References 28 publications

Copper brain homeostasis: Role of amyloid precursor protein and prion protein

Copper brain homeostasis: Role of amyloid precursor protein and prion protein

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

Amyloid precursor protein at node of Ranvier modulates nodal formation

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