Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction

Bolliger, Marc; Zurlinden, Andreas; Lüscher, Daniel; Bütikofer, Lukas; Shakhova, Olga; Francolini, Maura; Kozlov, Serguei; Cinelli, Paolo; Stephan, Alexander; Kistler, Andreas D.; Rülicke, Thomas; Pelczar, Pawel; Ledermann, Birgit; Fumagalli, Guido Francesco; Gloor, Sergio M.; Kunz, Beat; Sonderegger, P.

doi:10.1242/jcs.072090

Cited by 88 publications

(113 citation statements)

References 29 publications

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“…Previous experiments have shown that the z0 splicing isoform is at least 10–20 folds overrepresented over the insert baring splice isoforms (Western blots and internal analyses). The appearance of the z0 splicing variant of the C‐terminal agrin fragments in blood, however, represents the activity of neurotrypsin 42. Further, a vast amount of z0 isoform of agrin is present on the postsynaptic side, which is also cleavable by neurotrypsin.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Scherbakov

Knops

Ebner³

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

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BackgroundC‐terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub‐fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.MethodsPatients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m2) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA.ResultsCAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation.ConclusionsCAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.

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Section: Discussionmentioning

confidence: 99%

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Scherbakov

Knops

Ebner³

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

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“…CAF is also a peptide fragment cleaved from the nerve-derived protein agrin in neuromuscular remodeling. Normally, the agrin protein is important to maintaining the NMJ [173]. However, excessive cleavage of agrin by the enzyme neurotrypsin leads to functional disintegration at the NMJ [173,174].…”

Section: Circulating Biomarkersmentioning

confidence: 99%

Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment

2015

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Aging is often accompanied by declines in physical functioning which impedes older adults' quality of life, sense of independence, and ability to perform daily tasks. Age-related decreases in skeletal muscle quantity, termed sarcopenia, have traditionally been blamed for these physical decrements. However, recent evidence suggests that the quality of muscle tissue may be more functionally relevant than its quantity. 'Muscle quality' has been emerging as a means to elucidate and describe the intricate intramuscular changes associated with muscle performance in the context of aging and sarcopenia. While muscle quality has most commonly been defined in terms of muscle composition or relative strength, at the core, muscle quality really describes muscle's ability to function. Skeletal muscle displays a strong structure-function relationship by which several architectural characteristics factor into its functional capacity. This review describes the structural, physiological, and functional determinants of muscle quality at the tissue and cellular level, while also introducing other novel parameters such as sarcomere spacing and integrity, circulating biomarkers, and the muscle quality index. Muscle qualitative features are described from the perspective of how physical exercise may improve muscle quality in older adults. This broad, multidimensional perspective of muscle quality in the context of aging and sarcopenia offers comprehensive insights for consideration and integration in developing improved prognostic tools for research and clinical care, while also promoting translational approaches to the design of novel targeted intervention strategies designed to maintain function and mobility into late life.

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“…Agrin, plays a synaptic coordinator role by easing interpolation of a nerve terminal, clustering of AChRs and maturation of NMJs [5]. This review showcases the task of Agrin in restricting muscular atrophy in SMA by the stabilization of NMJs and thus delaying disease progression, muscle atrophy and also motor impairment.…”

Section: Role Of Agrinmentioning

confidence: 83%

Spinal muscular atrophy counteracted by Agrin biological NT-1654

Paul¹

2018

J Neurosci Neurol Disord

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Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction

Cited by 88 publications

References 29 publications

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment

Spinal muscular atrophy counteracted by Agrin biological NT-1654

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