IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Amytrophic lateral sclerosis- immunoglobulins selectively interact with neuromuscular junctions expressing P/Q- type calcium channels ?
Autor/es:
GONZALEZ LE; KOTLER MONICA L; VATTINO LUCAS; CONTI E.; REISIN RICARDO C; MULATZ KIK; SNUTCH TP; OSVALDO OD
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2011 vol. 119 p. 826 - 838
ISSN:
0022-3042
Resumen:
AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerativedisease characterized by a gradual loss of motoneurons.The majority of ALS cases are associated with a sporadic formwhose etiology is unknown. Several pieces of evidence favorautoimmunity as a potential contributor to sporadic ALSpathology. To gain understanding concerning possible antigensinteracting with IgGs from sporadic ALS patients (ALS?IgGs), we studied immunoreactivity against neuromuscularjunction (NMJ), spinal cord and cerebellum of mice with andwithout the CaV2.1 pore-forming subunit of the P/Q-typevoltage-gated calcium (Ca2+) channel. ALS?IgGs showed astrong reactivity against NMJs of wild-type diaphragms. ALS?IgGs also increased muscle miniature end-plate potentialfrequency, suggesting a functional role for ALS?IgGs onsynaptic signaling. In support, in mice lacking the CaV2.1subunit ALS?IgGs showed significantly reduced NMJ immunoreactivityand did not alter spontaneous acetylcholine release.This difference in reactivity was absent whencomparing N-type Ca2+ channel wild-type or null mice. Theseresults are particularly relevant because motoneurons areknown to be early pathogenic targets in ALS. Our findings addfurther evidence supporting autoimmunity as one of the possiblemechanisms contributing to ALS pathology. They alsosuggest that serum autoantibodies in a subset of ALS patientswould interact with NMJ proteins down-regulated when P/Qtypechannels are absent.Keywords: amyotrophic lateral sclerosis, autoantibodies,autoimmunity, calcium channels.J. Neurochem. (2011) 119, 826?838.JOURNAL OF NEUROCHEMISTRY | 2011 | 119 | 826?838 doi: 10.1111/j.1471-4159.2011.07462.x826 Journal of Neurochemistry 2011 International Society for Neurochemistry, J. Neurochem. (2011) 119, 826?838 2011 The Authors