Amyotrophic lateral sclerosis (ALS) is a lethal
neurodege
nerative disease characterized by progressive muscular atrophy, paralysis a
nd bulbar symptoms. Tra
nsge
nic mice over-expressi
ng huma
n muta
nt Cu/Z
n superoxide dismutase-1 (SOD1) mimicked the pathological phe
notype of ALS.
dl-
3-
n-
butylphthalide (
dl-NBP) has bee
n demo
nstrated to play a
neuroprotective role i
n cerebral ischemia, vascular deme
ntia, a
nd Alzheimer¡¯s disease. I
n the curre
nt study, we exami
ned the effect of
dl-NBP i
n Tg (SOD1-G9
3A) tra
nsge
nic mice, a well-studied model of ALS. Followi
ng the symptomatic o
nset of disease, oral admi
nistratio
n of
dl-NBP sig
nifica
ntly improved motor performa
nce, exte
nded the survival i
nterval, atte
nuated motor
neuro
n loss, a
nd delayed motor u
nit reductio
n compared to vehicle co
ntrols. These observatio
ns were further corroborated by the sig
nifica
nt reductio
n i
n immu
noreactivity of CD11b a
nd glial fibrillary acidic protei
n (GFAP), markers for microglia a
nd astrocytes, respectively. Additio
nally, dow
nregulatio
n of
nuclear factor ¦ÊB (NF-¦ÊB) p65 a
nd tumor
necrosis factor-¦Á (TNF-¦Á) protei
n levels a
nd a slight upregulatio
n of NF-E2-related factor 2 (Nrf2) a
nd heme oxyge
nase-1 (HO-1) were fou
nd i
n the spi
nal cord of Tg (SOD1-G9
3A) mice treated by
dl-NBP. These results suggest that
dl-NBP might be a promisi
ng compou
nd i
n the treatme
nt of ALS.
This article is part of a Special Issue entitled ¡®Post-Traumatic Stress Disorder?