TY - JOUR
T1 - Neurofilament protein levels
T2 - Quantitative analysis in essential tremor cerebellar cortex
AU - Louis, Elan D.
AU - Ma, Karen
AU - Babij, Rachel
AU - Cortés, Etty
AU - Liem, Ronald K.
AU - Vonsattel, Jean Paul G.
AU - Faust, Phyllis L.
PY - 2012/6/14
Y1 - 2012/6/14
N2 - Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28 ± 0.47 vs. 1.06 ± 0.32, p=0.02; and 1.38 ± 0.75 vs. 1.00 ± 0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET.
AB - Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28 ± 0.47 vs. 1.06 ± 0.32, p=0.02; and 1.38 ± 0.75 vs. 1.00 ± 0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET.
KW - Essential tremor
KW - Neurodegenerative
KW - Neurofilament proteins
KW - Pathophysiology
KW - Purkinje cell
KW - Western blot
UR - http://www.scopus.com/inward/record.url?scp=84861526694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861526694&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2012.04.054
DO - 10.1016/j.neulet.2012.04.054
M3 - Article
C2 - 22561033
AN - SCOPUS:84861526694
VL - 518
SP - 49
EP - 54
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -