PMID- 33925080 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20240402 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 9 DP - 2021 Apr 28 TI - Blood-Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration. LID - 10.3390/ijms22094661 [doi] LID - 4661 AB - Pathophysiology of chronic neurodegeneration is mainly based on complex mechanisms related to aberrant signal transduction, excitation/inhibition imbalance, excitotoxicity, synaptic dysfunction, oxidative stress, proteotoxicity and protein misfolding, local insulin resistance and metabolic dysfunction, excessive cell death, development of glia-supported neuroinflammation, and failure of neurogenesis. These mechanisms tightly associate with dramatic alterations in the structure and activity of the neurovascular unit (NVU) and the blood-brain barrier (BBB). NVU is an ensemble of brain cells (brain microvessel endothelial cells (BMECs), astrocytes, pericytes, neurons, and microglia) serving for the adjustment of cell-to-cell interactions, metabolic coupling, local microcirculation, and neuronal excitability to the actual needs of the brain. The part of the NVU known as a BBB controls selective access of endogenous and exogenous molecules to the brain tissue and efflux of metabolites to the blood, thereby providing maintenance of brain chemical homeostasis critical for efficient signal transduction and brain plasticity. In Alzheimer's disease, mitochondria are the target organelles for amyloid-induced neurodegeneration and alterations in NVU metabolic coupling or BBB breakdown. In this review we discuss understandings on mitochondria-driven NVU and BBB dysfunction, and how it might be studied in current and prospective NVU/BBB in vitro models for finding new approaches for the efficient pharmacotherapy of Alzheimer's disease. FAU - Salmina, Alla B AU - Salmina AB AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. AD - Research Center of Neurology, 125367 Moscow, Russia. FAU - Kharitonova, Ekaterina V AU - Kharitonova EV AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Gorina, Yana V AU - Gorina YV AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Teplyashina, Elena A AU - Teplyashina EA AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Malinovskaya, Natalia A AU - Malinovskaya NA AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Khilazheva, Elena D AU - Khilazheva ED AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Mosyagina, Angelina I AU - Mosyagina AI AUID- ORCID: 0000-0002-7344-7925 AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Morgun, Andrey V AU - Morgun AV AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Shuvaev, Anton N AU - Shuvaev AN AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Salmin, Vladimir V AU - Salmin VV AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Lopatina, Olga L AU - Lopatina OL AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. FAU - Komleva, Yulia K AU - Komleva YK AUID- ORCID: 0000-0001-5742-8356 AD - Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia. LA - eng GR - capital EN, Cyrilliccapital SHA, Cyrillic-2547.2020.7/Council on grants of the President of the Russian Federation/ PT - Journal Article PT - Review DEP - 20210428 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (DNA, Mitochondrial) RN - 0 (Reactive Oxygen Species) SB - IM MH - Alzheimer Disease/etiology/physiopathology MH - Animals MH - Blood-Brain Barrier/*physiopathology MH - DNA Damage MH - DNA, Mitochondrial/metabolism MH - Humans MH - In Vitro Techniques MH - Mitochondria/*physiology MH - *Models, Neurological MH - Nerve Degeneration/*etiology/*physiopathology MH - Neurodegenerative Diseases/etiology/physiopathology MH - Neurons/physiology MH - Reactive Oxygen Species/metabolism PMC - PMC8125678 OTO - NOTNLM OT - Alzheimer's disease OT - in vitro blood-brain barrier model OT - in vitro neurovascular unit model OT - mitochondria OT - neurodegeneration COIS- The authors declare no conflict of interest. EDAT- 2021/05/01 06:00 MHDA- 2021/05/25 06:00 PMCR- 2021/04/28 CRDT- 2021/04/30 01:30 PHST- 2021/04/10 00:00 [received] PHST- 2021/04/24 00:00 [revised] PHST- 2021/04/27 00:00 [accepted] PHST- 2021/04/30 01:30 [entrez] PHST- 2021/05/01 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2021/04/28 00:00 [pmc-release] AID - ijms22094661 [pii] AID - ijms-22-04661 [pii] AID - 10.3390/ijms22094661 [doi] PST - epublish SO - Int J Mol Sci. 2021 Apr 28;22(9):4661. doi: 10.3390/ijms22094661.