ABC Transporters at the BBB

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Historically, ABC transporters first gained doubtful fame as being responsible for the occurrence of chemoresistance, because some members of the ABC transporter family very efficiently expel almost all chemotherapeutics from tumour cells. This has pushed pharmacologic ABC transporter research toward the development of inhibitors to aid chemotherapies.

However, beside their protective function against xenobiotics and drugs ABC transporters also play an important role in excreting metabolites and toxic peptides from cells and organs. During the recent years, we were able to uncover the importance of the family members ABCB1 and ABCC1 for the clearance of toxic peptides from the brain that are known to trigger neurodegenerative diseases.
Thus, the activation of specific ABC transporters as a new treatment option and their utilisation in diagnostics is currently developed by us for different neurodegenerative diseases that have localised deposition of aggregating peptides (e.g. Alzheimer’s, Huntington’s, Lewy body dementia etc.).

* Newly established mouse models:

1. humanised ABCA7(floxed) MGI:6258226
2. humanised ABCC1(floxed) MGI:6258225

* Project Links:

Read more …  DFG ABC-LRP1 project
Read more …  NFR FRIMEDBIO 2016 project

* Published Research Papers (selection):

  • The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM
    Brain Behav Immun (2018)

    Storck SE, Hartz AMS, Bernard J, Wolf A, Kachlmeier A, Mahringer A, Weggen S, Pahnke J, Pietrzik CU
    73:21-33 PubMed PDF

  • ABCA7 downregulation modifies cellular cholesterol homeostasis and decreases Aβ peptide efflux in an in vitro model of the blood-brain barrier
    Journal of Alzheimer’s Disease (2018)

    Lamartinière Y, Boucau MC, Dehouck L, Krohn M, Pahnke J, Candela P, Gosselet F, Fenart L
    64(4):1195-1211 PubMed PDF

  • Humanization of the blood-brain barrier transporter ABCB1 in mice disrupts genomic locus – lessons from three unsuccessful approaches
    European J Microbiol Immunol (2018)

    Krohn M, Wanek T, Menet MC, Noack A, Declèves X, Langer O, Löscher L, Pahnke J
    8(3):78-86 PubMed PDF

  • Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula.
    Schizophrenia Res (2016)

    Bernstein HG, Hildebrandt J, Dobrowolny H, Steiner J, Bogerts B, Pahnke J
    Nov 177(1-3):52-58. PubMed PDF

  • Accumulation of murine β-amyloid mimics early Alzheimer’s disease.
    Brain (2015)

    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
    45(8):738-43. PubMed

  • 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)

    Hofrichter J*, Krohn M*, Schumacher T, Lange C, Feistel B, Walbroel B, Heinze HJ, Crockett S, Sharbel TF, Pahnke J
    Dec 10(10):1057-69. PubMed PDF

  • Impaired mitochondrial energy production and ABC transporter function – a crucial interconnection in dementing proteopathies of the brain.
    Mech Ageing Dev (2013)

    Pahnke J, Fröhlich Ch, Krohn M, Schumacher T, Paarmann K
    Oct 134(10):506-15. PubMed PDF

  • ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice.
    PLoSone (2012)

    Schumacher T, Krohn M, Hofrichter J, Lange C, Stenzel J, Steffen J, Dunkelmann T, Paarmann K, Fröhlich C, Uecker A, Plath AS, Sommer A, Brüning T, Heinze HJ, Pahnke J
    Apr 7(4):e35613. PubMed PDF

  • 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)

    Pahnke J, Walker L, Scheffler K, Krohn M
    Jul 33(7): 1099-1108. PubMed PDF

  • 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)

    Pahnke J, Wolkenhauer O, Krohn M, Walker LC
    Aug 5(4):396-405. PubMed PDF