The biomarkers of immune dysregulation and inflammation response in Parkinson disease

Parkinson’s disease(PD)is referring to the multi-systemicα-synucleinopathy with Lewy bodies deposited in midbrain.In ageing,the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration,especially in dopaminergic neurons.As a series of biomarkers,the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation.Furthermore,dopaminergic drugs change the biological characteristic of T lymphatic cells,affect theα-synuclein presentation pathway,and inhibit T lymphatic cells to release cytotoxicity in PD development.Taking together,the serum inflammatory factors and blood T cells are involved in the immune dysregulation of PD and inspected as the potential clinic biomarkers for PD prediction.

Peripheral Lymphocyte Subsets as a Marker of Parkinson's Disease in a Chinese Population

In this study, we conducted a clinical analysis of lymphocyte subtypes in 268 patients with Parkinson＇s disease （PD） to assess their clinical impact as a potential marker of advanced PD in Chinese patients. The participants comprised 268 sporadic PD patients and 268 healthy controls. The numbers of natural killer （NK） cells and CD3＋, CD3＋CD4＋, CD3＋CD8＋, and CD19＋ lympho- cytes from peripheral blood were determined by immunos- taining and flow cytometric analysis and the percentages of these CD＋ T cells were calculated. The ratio of regulatory T （Treg）/helper T 17 （Thl7） lymphocytes from 64 PD patients and 46 controls was determined by flow cytometric analysis. The results showed that the percentage of NK cells was higher in advanced PD patients than in controls （22.92% ± 10.08% versus 19.76% ±10.09%, P= 0.006）, while CD3＋ T cells are decreased （62.93% ±9.27% versus 65.75% ± 9.13%, P = 0.005）. The percentage of CD19＋ B cells in male patients was lower （P = 0.021） than in female patients, whereas NK cells were increased （P 〈 0.0001）. The scores on the Unified Parkinson＇s Disease Rating Scale （UPDRS） and the Non-Motor Symptoms Scale in late-onset PD patients were significantly higher than those in earlyonset patients （P = 0.024 and P = 0.007, respectively）. The percentage of CD19＋ B cells in patients with UPDRS scores 〉24 was lower than in those with scores 〈24 （10.17% ± 4.19% versus 12.22% ± 5.39%, P = 0.009）. In addition, the Treg/Th17 ratio in female patients was higher than that in female controls （13.88 ± 6.32 versus 9.94 ±4.06, P = 0.042）. These results suggest that the percentages of NK cells, CD3＋ T cells, and CD19＋ B cells along with the Treg/Th17 ratio in peripheral blood may be used to predict the risk of PD in Chinese individuals and provide fresh avenues for novel diagnostic biomarkers and therapeutic designs.

Whistle signal variations among three Indo-Pacific humpback dolphin populations in the South China Sea:a combined effect of the Qiongzhou Strait’s geographical barrier function and local ambient noise?

Geographic variations in the dolphin whistles could be useful in assessing association and isolation among populations.Whistle of free-ranging Indo-Pacific humpback dolphins(Sousa chinensis)among the Pearl River Estuary(PRE),Leizhou Bei(LZB)and Sanniang Bay(SNB)populations were investigated.A total of 2850 whistles with legible fundamental contour were extracted and 15 acoustic parameters were measured.Contrary to SNB,PRE and LZB had the same relative proportion of tonal type compositions with flat and sine representing the most frequent types.The generalized linear model analysis showed significant acoustic difference among populations and tonal types.All frequency parameters in SNB were significantly higher than those in PRE and LZB,where no significant variation was observed in most of the parameters either at the population level or within each tonal type.Canonical discriminant functions analysis showed a smaller difference between PRE and LZB than between PRE and SNB and between LZB and SNB.Compared with previous recordings,recent recordings demonstrated a consistent pattern of becoming higher in whistle frequency parameters in both LZB and SNB populations,suggesting that noise pollution in LZB and SNB increasing with time according to the acoustic niche hypothesis.Dolphin whistle’s geographic variations could be shaped by the combined function of the geographical barrier function of the Qiongzhou strait and local ambient noise.Considering the isolated condition and the relatively smaller population size of the humpback dolphin in the SNB,more effective and proactive conservation actions should be taken to prevent the extinction of small populations.

CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease

Background:Parkinson’s disease(PD)is the second most common neurodegenerative disease after Alzheimer’s dementia.Mitochondrial dysfunction is involved in the pathology of PD.Coiled-coil-helix-coiled-coil-helix domain-containing 2(CHCHD2)was identified as associated with autosomal dominant PD.However,the mechanism of CHCHD2 in PD remains unclear.Methods:Short hairpin RNA(ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma(SHSY5Y)and HeLa cells.Blue-native polyacrylamide gel electrophoresis(PAGE)and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system(MICOS).Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10.Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)administration were used to examine the influence of CHCHD2 in vivo.Results:We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium(MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model.Furthermore,we identified that CHCHD2 interacted with Mic10,and overexpression of CHCHD2 can protect against MPP+-induced MICOS impairment,while knockdown of CHCHD2 impaired the stability of MICOS.Conclusion:This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex,which contributes to protecting mitochondrial function in PD.