Uncoupling protein, a protein that participates in proton transport in the inner mitochondrial membrane, has some physiologic functions such as regulating thermogenesis, maintaining body temperature, regulating energy balance and adenosine triphosphate production, controlling reactive oxygen species production, and restraining apoptosis. It takes part in the pathophysiological processes in a number of diseases. The article reviews the uncoupling protein gene, distribution and regulation, the roles in peripheral tissues and central nervous system, and its possible relationship with cerebral infarction.

Objective To investigate the difference of cerebral inter-hemispheric functional connectivity between the patients with amyotrophic lateral sclerosis ( ALS) and healthy controls ( HC) by a newly developed voxel-mirrored homotopic connectivity ( VMHC) method based on resting-state functional MRI ( rs-fMRI) , as well as its correlation to the structural imaging indices and clinical neurological scales .Methods Twenty patients with ALS ( ALS group ) and 20 age-, and sex-matched healthy controls ( HC group) were examined by rs-fMRI and diffusion tensor imaging ( DTI ) on 3.0 T MR imaging system ( Siemens Trio Tim ).The rs-fMRI data preprocessing were performed using data processing assistant for rs-fMRI ( DPARSF) based on Matlab 2009a, and the rs-fMRI data analysis toolkit ( REST) with an automated VMHC approach was utilized to calculate and compare the VMHC correlation coefficients between the ALS group and the HC group[P<0.05, corrected with false discovery rate (FDR)].Region of interest (ROIs) were prescribed on the regions which showed abnormal VMHC coefficients in ALS group , then the mean time series of the ROIs were extracted to examine the difference of the seed ( ROIs)-based functional connectivity between the ALS and HC groups.At last, linear correlations were performed to assess the relationships among the VMHC coefficients and clinical measures including the revised amyotrophic lateral sclerosis functional rating scale ( ALSFRS-r) score, disease duration , the rate of disease progression and fractional anisotropy ( FA) values of the corpus callosum ( CC).Results Compared with HC group , the patients with ALS showed lower VMHC coefficients in the precentral gyrus ( M1 ) , postcentral gyrus ( PCG ) , inferior parietal lobule (IPL), cuneus/precuneus (Cu/Pcu), and anterior cingulate gyrus (ACC).Higher VMHC coefficients were found in the supplementary motor area , superior frontal gyrus , and middle occipital gyrus (P<0.05,FDR corrected).Significant functional connectivity alterations were detected in motor cortex and frontal/temporal/occipital lobe between the ALS and HC groups using seed ( ROIs )-based functional connectivity based on the regions which showed abnormal VMHC coefficients in ALS group ( P <0.05, AlphaSim corrected, clusters≥228 voxels).Significant positive correlation was detected between the VMHC coefficients (0.311 ±0.108) of M1 and FA values (0.394 ±0.016) of CC III region (r=0.530, P=0.016), between the VMHC coefficients (0.767 ±0.043) of ACC and FA values (0.360 ±0.105) of CC I region (r=0.513, P=0.021), respectively.Significant positive correlation was observed between VMHC coefficients (0.311 ±0.108) of M1 and the ALSFRS-r score (35.4 ±2.5) in ALS patients(r=0.447, P=0.048).There was not significant correlation observed between the VMHC coefficients and disease duration , or the ratio of disease prognosis (P>0.05).Conclusions Abnormal VMHC coefficients were detected in ALS patients.The decreased VMHC in ACC and M1 are associated with the reduced micro-structure integrity of CC, meanwhile, and they may be related to disease severity.