Roles and Mechanisms of the Protein Quality Control System in Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the deposition of senile plaques (SPs) and the formation of neurofibrillary tangles (NTFs), as well as neuronal dysfunctions in the brain, but in fact, patients have shown a sustained disease progression for at least 10 to 15 years before these pathologic biomarkers can be detected. Consequently, as the most common chronic neurological disease in the elderly, the challenge of AD treatment is that it is short of effective biomarkers for early diagnosis. The protein quality control system is a collection of cellular pathways that can recognize damaged proteins and thereby modulate their turnover. Abundant evidence indicates that the accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system. In particular, it is the synthesis, degradation, and removal of essential biological components that have already changed in the early stage of AD, which further encourages us to pay more attention to the protein quality control system. The review mainly focuses on the endoplasmic reticulum system (ERS), autophagy–lysosome system (ALS) and the ubiquitin–proteasome system (UPS), and deeply discusses the relationship between the protein quality control system and the abnormal proteins of AD, which can not only help us to understand how and why the complex regulatory system becomes malfunctional during AD progression, but also provide more novel therapeutic strategies to prevent the development of AD.

Development of a centralized approach to conducting interlaboratory proficiency tests

Важнейшим звеном системы контроля качества нефти являются испытательные лаборатории, от компетентности которых зависит достоверность результатов измерений и эффективность управленческих решений, принимаемых с учетом полученных данных. Одним из способов подтверждения достоверности результатов измерений является проверка квалификации лаборатории посредством ее участия в межлабораторных сличительных (сравнительных) испытаниях (МСИ). В настоящей статье рассмотрены вопросы проведения таких испытаний для лабораторий организаций системы «Транснефть». Описан действующий порядок, предполагающий участие лабораторий в МСИ в регионах своего местонахождения, при этом разработкой и реализацией программы проверки квалификации занимаются сторонние организации - провайдеры МСИ. Такая практика имеет существенные недостатки, не позволяя, в том числе, систематизировать и обобщить результаты МСИ для общей оценки деятельности испытательных лабораторий ПАО «Транснефть». В статье представлен централизованный подход к проведению МСИ в ПАО «Транснефть», устанавливающий единый порядок участия лабораторий в испытаниях с целью осуществления общей оценки квалификации лабораторий, своевременной разработки и реализации предупреждающих и корректирующих мероприятий по улучшению деятельности лабораторий, усовершенствования системы контроля качества нефти на объектах ПАО «Транснефть». The most important link in the oil quality control system are testing laboratories, the competence of which determines the reliability of measurement results and the effectiveness of management decisions based on the data obtained. One way to confirm the validity of measurement results is to verify the laboratory qualifications through its participation in interlaboratory proficiency (comparative) tests (IPT). This article considers the issues of such tests for the laboratories of Transneft system entities. The current procedure is described, which involves the participation of laboratories in the IPT in the regions of their location, while the development and implementation of the proficiency testing program is carried out by third-party IPT provider organizations. This practice has significant drawbacks, not allowing, among other things, to systematize and summarize the results of IPT for an overall assessment of the activities of Transneft PJSC’s testing laboratories. The article presents a centralized approach to conducting IPT in Transneft PJSC, which establishes a unified procedure for the participation of laboratories in tests in order to implement an overall assessment of laboratory qualification, timely development and implementation of preventive and corrective measures to improve the performance of laboratories and improve the oil quality control system at the Transneft PJSC facilities.

FUNCTIONAL MAPPING OF THE MEDICINES’ QUALITY CONTROL SYSTEM PROCESSES IN THE SVERDLOVSK REGION

The article describes the results of subject-object and risk-based mapping of the medicines’ quality control system. Identification and procedural structuring of key processes of drug quality control systems in Russia was carried out. The matrix of key procedures was formed in coordinates of agency, target, time, and level characteristics for qualitative mapping of the processes and procedures. To quantify the control measures modality in the coordinates "product-context", the structural coefficient of distribution of procedures was calculated for each section of the commodity distribution network: the product emphasis in the production/ manufacturing segment and the environmental emphasis in the system of market distribution of medicines. Based on the results of risk-based mapping, it was determined that the segments of wholesale and retail pharmaceutical activities are characterized by a shift in control measures to the segment of external reactive procedures, which seems to be a negative trend. It is shown that the production of medicines is the leading segment in the implementation of risk-based quality control procedures for medicines, while in the wholesale and retail trade segment this indicator is 95% lower. The key target for optimization measures is the regional wholesale and retail segment of the pharmaceutical market due to the risk-based selective approach to checking compliance with licensing requirements and a large number of control objects.