Urine proteome changes in an α-synuclein transgenic mouse model of Parkinson’s disease

Abstract

Urine accommodates more changes than other fluids, and it is a good source in the search for early sensitive biomarkers. The present study collected urine samples from 2-, 4-, 6-, 8-and 10-month-old αsynuclein transgenic mice. Based on data-independent acquisition (DIA) technology, liquid chromatographytandem mass spectrometry (LC-MS/MS) was used for quantitative analysis. Seventeen human homologous differential proteins were screened and compared with those in the urine of 2-month-old mice, and 9 proteins were related to Parkinson's disease (PD). Formin-2, Splicing factor 3A subunit 1, and Isopentenyl-diphosphate Deltaisomerase 1 changed continuously in months 6, 8 and 10. These experiments and analyses demonstrated that the urine proteome reflected the development of α-synuclein transgenic mice and provided clues for the early clinical diagnosis of PD. Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive motor and non-motor disorders [1]. Its main pathological features are the progressive loss of dopaminergic neurons in the dense substantia nigra and the presence of α-synuclein as the main component of eosinophilic inclusion bodies, i.e., Lewy bodies, in the remaining dopaminergic neurons. PD is the second most common neurodegenerative disease, and it affects approximately 1% of people over 65 years of age [2]. With the aging of the population and the prolongation of life expectancy, the incidence rate of PD is expected to double in the next 20 years [3]. PD seriously affects the quality of life of patients, and it results in a huge social and economic burden [4, 5]. The early diagnosis of PD is of great significance to improve the quality of life of patients and delay the development of the disease. There is no effective way to cure PD. Drug therapy and surgical treatment only delay the progress of the disease. Drug therapy is the primary method, but the long-term use of drugs often weakens the curative effects and produces some side effects. The clinical diagnosis of PD is currently based on motor characteristics. When the motor characteristics of PD manifest, approximately 60-70% of the neurons are lost [6]. Because the early symptoms of PD are mild and generally considered the result of aging, the early diagnosis of PD is very difficult, and there is a certain rate of misdiagnosis. At the time of diagnosis, most patients exhibit obvious behavior disorders and accumulated pathological changes. Therefore, to provide better clinical treatment for PD patients and help researchers find new treatment methods, it is urgent to identify sensitive early biomarkers. Biomarkers are indicators that objectively reflect normal physiological and pathological processes [7]. The most studied biomarkers are present in blood and cerebrospinal fluid. Because there is no barrier between the cerebrospinal fluid and the brain, cerebrospinal fluid is considered an ideal choice for the discovery of biomarkers of neurodegenerative diseases. Cerebrospinal fluidis more stable than blood due to the blood-...

Urine proteome changes in a chronic unpredictable mild stress (CUMS) mouse model of major depressive disorder

“…We also compared the urinary differential proteins in the CUMS model to those in 15 other models, including a clinical model of autism [62] and a variety of animal models of Alzheimer's disease [11], Parkinson's disease [12], myocarditis [63] , chronic pancreatitis [64], unilateral ureteral obstruction model [65], astrocytoma [66], liver fibrosis [67] , pulmonary fibrosis [68] , glomerulosclerosis [69] , a model involving the injection of 10 tumor cells [70], the Walker-256 intracerebral tumor model [71], the Walker-256 liver tumor model [72], the Walker-256 subcutaneous model [73] and the Walker-256 lung metastasis model [74]. The comparison results are presented in Table S6.…”

“…In brief, the C57BL/6 male mice were divided into the control group (n=20) and the CUMS group (n=12). Then, the CUMS group was exposed to a variety of mild stressors: (1) overnight light exposure, (2) darkness for 12 h, (3) wet bedding for 12 h, (4) removal of bedding for 12 h, (5) tilting of the cage (45°) for 12 h, (6) deprivation of food for 12 h, (7) deprivation of water for 12 h, (8) soaking for 3 min in cold water (4 °C), ( 9) soaking for 3 min in water at 45 °C, (10) physical restraint for 4 h, (11) exposure to the smell of cats for 3 h, (12) exposure to the sound of cats for 3 h, (13) cage vibration (80 rpm) for 3 h, ( 14) strobe lighting for 3 h, (15) and electrical shocks to the feet for 15 min (0.2 mA). The CUMS group was randomly subjected to the various stressors repeatedly for a period of five weeks.…”

“…In our previous studies, early candidate urine biomarkers could be detected successfully before b-amyloid deposition in a APP/PS1 transgenic mouse model of Alzheimer's disease (AD) [11]. In addition, several urinary differential proteins were screened in an a-synuclein transgenic mouse model of Parkinson's disease (PD) [12]. Since recent evidence suggests that there is a strong relationship between MDD and neurodegenerative diseases such as AD and PD [13,14], we therefore aimed to determine whether the urine proteome can reflect changes associated with MDD.…”

Urine proteome changes in a chronic unpredictable mild stress (CUMS) mouse model of major depressive disorder

“…We also compared the urinary differential proteins in the CUMS model to those in 15 other models, including a clinical model of autism [62] and a variety of animal models of Alzheimer's disease [11], Parkinson's disease [12], myocarditis [63] , chronic pancreatitis [64], unilateral ureteral obstruction model [65], astrocytoma [66], liver fibrosis [67] , pulmonary fibrosis [68] , glomerulosclerosis [69] , a model involving the injection of 10 tumor cells [70], the Walker-256 intracerebral tumor model [71], the Walker-256 liver tumor model [72], the Walker-256 subcutaneous model [73] and the Walker-256 lung metastasis model [74]. The comparison results are presented in Table S6.…”

The Latest Developments in Using Proteomic Biomarkers from Urine and Serum for Non-Invasive Disease Diagnosis and Prognosis

“…Li et al using the urine proteome of transgenic mice, reflected the early clinical diagnosis of PD by following proteins: Formin-2, Splicing factor 3A subunit 1, and Isopentenyldiphosphate Deltaisomerase 1 by employing quantitative LC-MS/MS. 80 In another study, due to the contradictory findings regarding the overall change in total α-syn levels between individuals with Parkinson's disease (PD) and control subjects, researchers have directed their attention toward investigating specific forms of α-syn as potential biomarkers. These specific forms include oligomeric α-syn, phosphorylated α-syn and nitrated α-syn.…”