A decline in the activities of oxidative phosphorylation(OXPHOS)complexes has been consistently reported in amyotrophic lateral sclerosis(ALS)patients and animal models of ALS,although the underlying molecular mechani...A decline in the activities of oxidative phosphorylation(OXPHOS)complexes has been consistently reported in amyotrophic lateral sclerosis(ALS)patients and animal models of ALS,although the underlying molecular mechanisms are still elusive.Here,we report that receptor expression enhancing protein 1(REEP1)acts as an important regulator of complex IV assembly,which is pivotal to preserving motor neurons in SOD1^(G93A) mice.We found the expression of REEP1 was greatly reduced in transgenic SOD1^(G93A) mice with ALS.Moreover,forced expression of REEP1 in the spinal cord extended the lifespan,decelerated symptom progression,and improved the motor performance of SOD1^(G93A) mice.The neuromuscular synaptic loss,gliosis,and even motor neuron loss in SOD1^(G93A) mice were alleviated by increased REEP1 through augmentation of mitochondrial function.Mechanistically,REEP1 associates with NDUFA4,and plays an important role in preserving the integrity of mitochondrial complex IV.Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.展开更多
Hereditary spastic paraplegia （HSP）, also known as familial spastic paraparesis or Stumpell-Lorrain disease, is a large group of inherited, heterogeneous neurologic disorders caused by the degeneration of corticosp...Hereditary spastic paraplegia （HSP）, also known as familial spastic paraparesis or Stumpell-Lorrain disease, is a large group of inherited, heterogeneous neurologic disorders caused by the degeneration of corticospinal axons. The prevalence is estimated at 3-10 cases per 100000 people in Europe, and is uncertain in other continents. Most patients have the same core features, which are characterized by spastic gait, lower limb hypertonicity, hyperreflexia, extensor-plantar responses, muscle weakness, and occasionally decreased vibration sense at the ankles, bladder dysfunction, pes cavus, or scoliosis.展开更多
基金supported by Shandong Key R&D Program Funding(2018GSF118037)the Shandong Natural Science Foundation(ZR2019JQ24).
文摘A decline in the activities of oxidative phosphorylation(OXPHOS)complexes has been consistently reported in amyotrophic lateral sclerosis(ALS)patients and animal models of ALS,although the underlying molecular mechanisms are still elusive.Here,we report that receptor expression enhancing protein 1(REEP1)acts as an important regulator of complex IV assembly,which is pivotal to preserving motor neurons in SOD1^(G93A) mice.We found the expression of REEP1 was greatly reduced in transgenic SOD1^(G93A) mice with ALS.Moreover,forced expression of REEP1 in the spinal cord extended the lifespan,decelerated symptom progression,and improved the motor performance of SOD1^(G93A) mice.The neuromuscular synaptic loss,gliosis,and even motor neuron loss in SOD1^(G93A) mice were alleviated by increased REEP1 through augmentation of mitochondrial function.Mechanistically,REEP1 associates with NDUFA4,and plays an important role in preserving the integrity of mitochondrial complex IV.Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.
基金This work was supported by grants from the National Basic Research Program of China （No. 2006CB500700）, National Hi-Tech Research and Development Program of China （No. 2004AA227040）, National Key Technologies Research and Development Program of China （No. 2004BA720A03）, National Natural Science Foundation of China （No. 30671151）, and Distinguished Youth Foundation of Hunan province （No. 2007JJ 1005）.
文摘Hereditary spastic paraplegia （HSP）, also known as familial spastic paraparesis or Stumpell-Lorrain disease, is a large group of inherited, heterogeneous neurologic disorders caused by the degeneration of corticospinal axons. The prevalence is estimated at 3-10 cases per 100000 people in Europe, and is uncertain in other continents. Most patients have the same core features, which are characterized by spastic gait, lower limb hypertonicity, hyperreflexia, extensor-plantar responses, muscle weakness, and occasionally decreased vibration sense at the ankles, bladder dysfunction, pes cavus, or scoliosis.
