At the brain’s barriers, import mechanisms for nutrition and exporting proteins are strictly regulated. The restriction of entry of undesirable agents is mainly achieved by restriction of paracellular flow and a high abundance of a range of ABC transporters. These proteins are also needed for the excretion of metabolic waste products from the brain, which is why the integrity of the brain’s barriers is not only important for the protection from exogenic threads but also for the maintenance of a physiologically balanced and functional brain.
We are working on new methods that would enable one to determine the functionality of these barriers in an individualized manner. Furthermore, we are developing treatments that enhance and restore the activity of ABC transporters to prevent and treat neurodegenerative diseases like Alzheimer’s disease.
* Project Links:
* Published Research Papers (selection):
Age-related ultrastructural changes of the basement membrane in the mouse blood-brain barrier
Journal of Cellular and Molecular Medicine (2019)
The choroid plexus in health and in disease: dialogues into and out of the brain
Neurobiology of Disease (2017)
Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula.
Schizophrenia Res (2016)
Accumulation of murine β-amyloid mimics early Alzheimer’s disease.
Krohn M, Bracke A, Avchalumov Y, Schumacher T, Hofrichter J, Paarmann K, Fröhlich C, Lange C, Brüning T, von Bohlen und Halbach O, Pahnke J
Aug 138(Pt 8):2370-82. PubMed
Cerebral ABC transporters: Common mechanisms may modulate neurodegenerative diseases and depression in elderly.
Arch Med Res (2014)
Pahnke J, Fröhlich C, Krohn M, Paarmann K, Bogdanovic N, Årsland D, Winblad B
Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary.
Mech Ageing Dev (2014)
Bernstein HG, Hölzl G, Dobrowolny H, Hildebrand J, Trübner K, Krohn M, Bogerts B, Pahnke J
Sep 141-142C:12-21. PubMed
Alzheimer’s and ABC transporters – new opportunities for diagnostics and treatment.
Neurobiol Dis (2014)
Pahnke J, Langer O, Krohn M
Dec 72 (2014) 54–60. PubMed
Reduced Alzheimer’s disease pathology by St. John’s wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice.
Curr Alz Res (2013)
Impaired mitochondrial energy production and ABC transporter function – a crucial interconnection in dementing proteopathies of the brain.
Mech Ageing Dev (2013)
ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice.
Cerebral amyloid-ß proteostasis is regulated by the membrane transport protein ABCC1 in mice.
J Clin Invest (2011)
Krohn M, Lange C, Hofrichter J, Scheffler K, Stenzel J, Steffen J, Schumacher T, Brüning T, Plath AS, Alfen F, Schmidt A, Winter F, Rateitschak K, Wree A, Gsponer J, Walker LC, Pahnke J
Oct 121(10):3924–3931. PubMed PDF
Alzheimer’s disease and blood-brain barrier function – Why have anti-beta-amyloid therapies failed to prevent dementia progression?
Neurosci Biobehav Rev (2009)
Die Funktion der Blut-Hirn-Schranke für die Pathogenese der Alzheimer Demenz – Implikationen für immunologische Therapien zur Plaqueauflösung.
Fortschr Neurol Psyc (2009)
Pahnke J, Krohn M, Scheffler K
Aug 77: S21-24. PubMed
Clinico-pathologic function of cerebral ABC transporters – implications for the pathogenesis of Alzheimer’s disease.
Curr Alz Research (2008)