STUDY DESIGN: Observational cross-section study. OBJECTIVE: The objective of our study was to determine if phosphorylation of aggregated neurofilaments (NFs) would occur in autoimmune-mediated motor neuron injury. Our main hypothesis was that autoimmune-mediated damage of spinal cord motor neurons may influence NF phosphorylation and lead to NF aggregation. METHODS: A total of 20 guinea pigs were inoculated with bovine spinal cord anterior horn homogenates (experimental autoimmune gray matter model) and 20 guinea pigs were inoculated with phosphate-buffered saline (control). NF phosphorylation and aggregation were observed by immunohistochemistry and electron microscopic examination. Data were analyzed using Student's t-test with P<0.05 being considered significant. RESULTS: Abnormal phosphorylation and distribution of NF occurred in motor neurons and axons of animals with experimental autoimmune gray matter disease but not in the control animals. CONCLUSION: Aberrant accumulation and phosphorylation of neurofilaments in perikarya of spinal cord motor neurons occur in immune-mediated motor neuron death. As both immunologic response and alteration of neurofilaments are observed in amyotrophic lateral sclerosis (ALS) patients and aberrant neurofilament change harms motor neurons, our present findings suggest that autoimmunity-induced ALS may mediate in part through neurofilament modification.
STUDY DESIGN: Observational cross-section study. OBJECTIVE: The objective of our study was to determine if phosphorylation of aggregated neurofilaments (NFs) would occur in autoimmune-mediated motor neuron injury. Our main hypothesis was that autoimmune-mediated damage of spinal cord motor neurons may influence NF phosphorylation and lead to NF aggregation. METHODS: A total of 20 guinea pigs were inoculated with bovine spinal cord anterior horn homogenates (experimental autoimmune gray matter model) and 20 guinea pigs were inoculated with phosphate-buffered saline (control). NF phosphorylation and aggregation were observed by immunohistochemistry and electron microscopic examination. Data were analyzed using Student's t-test with P<0.05 being considered significant. RESULTS: Abnormal phosphorylation and distribution of NF occurred in motor neurons and axons of animals with experimental autoimmune gray matter disease but not in the control animals. CONCLUSION: Aberrant accumulation and phosphorylation of neurofilaments in perikarya of spinal cord motor neurons occur in immune-mediated motor neuron death. As both immunologic response and alteration of neurofilaments are observed in amyotrophic lateral sclerosis (ALS) patients and aberrant neurofilament change harms motor neurons, our present findings suggest that autoimmunity-induced ALS may mediate in part through neurofilament modification.
Authors: Raghothama Chaerkady; Candace L Kerr; Arivusudar Marimuthu; Dhanashree S Kelkar; Manoj Kumar Kashyap; Marjan Gucek; John D Gearhart; Akhilesh Pandey Journal: J Proteome Res Date: 2009-03 Impact factor: 4.466
Authors: Amanda K Engstrom; Alicia C Walker; Rohitha A Moudgal; Dexter A Myrick; Stephanie M Kyle; Yu Bai; M Jordan Rowley; David J Katz Journal: Proc Natl Acad Sci U S A Date: 2020-11-02 Impact factor: 11.205