ErbB2pY -1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification.

AIMS: This study aims to reveal a promising biomarker for Parkinson's disease (PD) based on research with reverse phase protein array (RPPA) technology for the first time and in vivo verification, which gains time for early intervention in PD, thus increasing the effectiveness of treatment and reducing disease morbidity. METHODS AND RESULTS: We employed RPPA technology which can assess both total and post-translationally modified proteins to identify biomarker candidates of PD in a cellular PD model. As a result, the phosphorylation (pY-1248) of the epidermal growth factor receptor (EGFR) ErbB2 is a promising biomarker candidate for PD. In addition, lapatinib, an ErbB2 tyrosine kinase inhibitor, was used to verify this PD biomarker candidate in vivo. We found that lapatinib-attenuated dopaminergic neuron loss and PD-like behavior in the zebrafish PD model. Accordingly, the expression of ErbB2pY-1248 significantly increased in the MPTP-induced mouse PD model. Our results suggest that ErbB2pY-1248 is a predictive biomarker for PD. CONCLUSIONS: In this study, we found that ErbB2pY-1248 is a predictive biomarker of PD by using RPPA technology and in vivo verification. It offers a new perspective on PD diagnosing and treatment, which will be essential in identifying individuals at risk of PD. In addition, this study provides new ideas for digging into biomarkers of other neurodegenerative diseases.

Low-frequency transcranial magnetic stimulation protects cognition in mice with chronic unpredictable mild stress through autophagy regulation.

Although transcranial magnetic stimulation (TMS) has been approved for the treatment of major depression, few studies have analyzed the ability of low-frequency TMS (LF-TMS) to treat depressive symptoms. Our study confirmed that LF-TMS protects the cognitive function,which can play a certain reference role in the future clinical treatment. The effectiveness of high-frequency TMS therapy has been well documented. However, the use of low-frequency TMS (LF-TMS) in the treatment of depression is rarely reported. This study aims to evaluate whether LF-TMS can reverse depression-induced cognitive impairment. We created a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Male C57BL/6J mice,6-8 weeks old,were randomly divided into four groups: a CON (control) group, a CUMS group, a CUMS+LF-TMS group, and a CUMS+LF-TMS+RAP (rapamycin) group. The CUMS was maintained for 28 days. LF-TMS (1 Hz) and Rap were administered for 28 days from the first day of CUMS. The mice in all groups except the control demonstrated evidence of anhedonia, anxiety, and cognitive decline on behavioral tests during the four weeks of CUMS.All the experiments were carried out under a 12-h light/dark cycle (lights on at 7 a.m.) except for the dark/light cycle reversal stimulation of CUMS. LF-TMS at 20 Mt, 1 Hz for 1 min alleviated damage to spatial cognition and synaptic plasticity in the hippocampus. Western blot analysis showed that LF-TMS reduced the down-regulation of autophagy signals in the CUMS+LF-TMS group, and enhanced the expression of synaptic plasticity-related factors, thereby improving the spatial cognitive impairment resulting from the CUMS. We concluded that LF-TMS can effectively relieve depressive behavior and cognitive dysfunction in mice subjected to CUMS by regulating autophagy signals and synaptic proteins.

Potential implications of polyphenolic compounds in neurodegenerative diseases.

Neurodegenerative diseases are common chronic diseases related to progressive damage to the nervous system. Current neurodegenerative diseases present difficulties and despite extensive research efforts to develop new disease-modifying therapies, there is still no effective treatment for halting the neurodegenerative process. Polyphenols are biologically active organic compounds abundantly found in various plants. It has been reported that plant-derived dietary polyphenols may improve some disease states and promote health. Emerging pieces of evidence indicate that polyphenols are associated with neurodegenerative diseases. This review aims to overview the potential neuroprotective roles of polyphenols in most common neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and ischemic stroke.