Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis （MS）, a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system （CNS）. Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis （EAE, a mouse model of MS）. Dysfunction of mitochondria that intensively influences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene （ATG） 5 and immune-related GTPase M （IRGM） 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin （mTOR）, ameliorates relapsing-remitting EAE. Inflammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-11/LC3-1 ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-inflammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinflammation associated with the pathogenesis of MS.
Parkinson＇s disease （PD） is the second most common neurodegenerative disorder affecting more than 1% of the older population. Histopathologically, PD is characterized by a severe loss of dopaminergic neurons in the substantia nigra and cytoplasmic inclusions composed of insoluble protein aggregates （Lewy bodies）, which lead to a pro- gressive movement disorder including the classic triad of tremor, bradykinesia, and rigidity.
Parkinson＇s disease （PD） is a complex neurode- generative disease with progressive loss of dopamine neurons. PD patients usually manifest a series of motor and non-motor symptoms. In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients, there is an urgent need to identify sensitive and specific biomarkers. Biomarkers can be divided into four categories： clinical, imaging, biochemical, and genetic. Ideal biomarkers not only improve our under- standing of PD pathogenesis and progression, but also provide benefits for early risk evaluation and clinical diagnosis of PD. Although many efforts have been made and several biomarkers have been extensively investigated, few if any have been found useful for early diagnosis. Here, we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.
Parkinson＇s disease （PD） is the second most common age-related neurodegenerative disorder after Alzheimer＇s disease. To date, the clinical diagnosis of PD is primarily based on the late onset of motor impairments. Unfortunately, at this stage, most of the dopaminergic neurons may have already been lost, leading to the limited clinical benefits of current therapeutics. Therefore, early identification of PD, especially at the prodromal stage, is still a main challenge in the diagnosis and management of this disease. Recently, microRNAs （miRNAs） in cerebrospinal fluid or peripheral blood have been proposed as putative biomarkers to assist in PD diagnosis and therapy. In this review, we systematically summarize the changes of miRNA expression profiles in PD patients, and highlight their putative roles in the diagnosis and treatment of this devastating disease.
Background:Neuron-microglia communication plays a crucial role in the motor neurons(MNs)death in amyotrophic lateral sclerosis(ALS).Neurons can express chemokine(C-X3-C motif)ligand 1(CX3CL1),which mediates microglial activation via interacting with its sole receptor CX3CR1 in microglia.In the present study,we aimed to investigate the dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and MNs loss in SOD1G93A mouse model of ALS.Methods:qPCR,western blot and immunofluorescent staining were used to examine the mRNA and protein levels and localization of CX3CL1/CX3CR1 in the anterior horn region of spinal cord in both SOD1G93A mice and their agematched wild type(WT)littermates at 40,60,90 and 120 days of age.The M1/M2 microglial activation in the spinal cord tissues of SOD1G93A mice and WT mice were evaluated by immunofluorescent staining of M1/M2 markers and further confirmed by qPCR analysis of M1/M2-related cytokines.Results:The immunofluorescent staining revealed that CX3CL1 was predominately expressed in MNs,while CX3CR1 was highly expressed in microglia in the anterior horn region of spinal cord.Compared with age-matched WT mice,CX3CL1 mRNA level was elevated at 40 days but decreased at 90 and 120 days in the anterior horn region of spinal cords in ALS mice.Consistently,CX3CR1 mRNA level was increased at 90 and 120 days.Western blot assay further confirmed the dynamic changes of CX3CL1/CX3CR1 axis in ALS mice.Additionally,the levels of M1/M2 markers of microglia and their related cytokines in the anterior horn region of spinal cord in ALS mice were increased at 90 and 120 days.Moreover,while M1-related cytokines in ALS mice were persistently increased at 120 days,the upregulated M2-related cytokines started to decline at 120 days,suggesting an altered microglial activation.Conclusions:Our data revealed the dynamic changes of CX3CL1/CX3CR1 axis and an imbalanced M1/M2 microglial activation during ALS pathological progression.These findings may help identify potential molecular targets for ALS th
Jingjing ZhangYufei LiuXinyao LiuSong LiCheng ChengSheng ChenWeidong Le
Hyposmia, identified as reduced sensitivity to odor, is a common non-motor symptom of Parkinson＇s disease （PD） that antedates the typical motor symptoms by several years. It occurs in -90% of early-stage cases of PD. In addition to the high prevalence, the occurrence of hyposmia may also predict a higher risk of PD. Investigations into hyposmia and its relationship with PD may help elucidate the underlying pathogenic mechanisms. This review provides an update of olfactory dysfunction in PD and its potential as a biomarker for this devastating disease.
