Tiina M. Kauppinen, Ph.D. (Maiden name: Tikka)
||Adjunct Assistant Professor
|In Lab Since:
The focus of my research is to understand the molecular signaling and effector pathways involved in microglial
activation, and the impact of these on neurodegeneration and neurogenesis. This work has recently focused on
poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is a nuclear enzyme that is involved in single strand DNA
repair. When activated, PARP-1 consumes NAD in order to produce ADP-riboses and over- /hyper-activation
of PARP-1 leads to energy depletion. Thus in pathologies including robust DNA damage (e.g. ischemic stroke)
inhibition of PARP-1 has been shown to improve neuronal survival. PARP-1 also functions as a co-activator of
transcription factors, such as NF-kB. This function of PARP-1 has been considered to be responsible for PARP-1's
ability to regulate inflammatory responses, including microglial activation. Microglial activation and inflammatory
responses in general can enhance neurodegeneration and reduce neurogenesis (attenuate survival of progenitor cells
or even reduce progenitor cell proliferation).
I see PARP-1 is as a critical integrating factor in neurodegeneration, neuroinflammation and neurogenesis, and
thus potential target for therapeutic approaches. It is important to aim towards better understanding of PARP-1's
role and regulation.
- Effects of energy supplementation on PARP-1-mediated cell death
- Neurogenesis and microglial activation
- PARP-1 mediated regulation of microglial function
- The molecular pathways leading to PARP-1 activation after inflammatory stimuli
- The gross-regulation between PARP-1 and MAPK
- Minocycline’s effect on PARP-1 activation
- The role of PARG in PARP-1 regulation
receptors regulate expression, phosphorylation and accumulation of
neurofilaments in spinal cord neurons. Neuroscience.
J, Tikka T,
Keinanen R, Goldsteins G, Chan PH, Koistinaho J.
A tetracycline derivative, minocycline, reduces inflammation
and protects against focal cerebral ischemia with a wide therapeutic
window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500.
Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J.
Minocycline, a tetracycline derivative, is neuroprotective
against excitotoxicity by inhibiting activation and proliferation of
microglia. J Neurosci. 2001 Apr 15;21(8):2580-8.
Koistinaho JE. Minocycline provides
neuroprotection against N-methyl-D-aspartate neurotoxicity by
inhibiting microglia. J Immunol. 2001 Jun 15;166(12):7527-33.
Usenius T, Tenhunen M, Keinanen R, Koistinaho J.
Tetracycline derivatives and ceftriaxone, a cephalosporin
antibiotic, protect neurons against apoptosis induced by ionizing
radiation. J Neurochem. 2001 Sep;78(6):1409-14.
Vartiainen NE, Goldsteins G, Oja SS, Andersen PM, Marklund SL,
Minocycline prevents neurotoxicity induced by cerebrospinal
fluid from patients with motor neurone disease. Brain. 2002
M, Garnier P, Kauppinen T,
Swanson R. Heat shock - induced Hsp70
expression in murine astrocytes does not require poly(ADP-ribose)
polymerase activity. Cell Physiol Biochem. 2003;13(5):297-300.
J, Yrjanheikki J, Kauppinen T,
Tetracycline derivatives as anti-inflammatory agents and
potential agents in stroke treatment. Ernst Schering Res Found
Workshop. 2004;(47):101-15. Review.
RA, Ying W, Kauppinen TM.
Astrocyte influences on ischemic neuronal death. Curr Mol
Med. 2004 Mar;4(2):193-205. Review.
Swanson RA. Poly(ADP-ribose) polymerase-1
promotes microglial activation, proliferation, and matrix
metalloproteinase-9-mediated neuron death. J Immunol. 2005 Feb
Suh SW, Genain CP, Swanson RA.
Poly(ADP-ribose) polymerase-1 activation in a primate model
of multiple sclerosis. J Neurosci Res. 2005 Jul 15;81(2):190-8.
Chan WY, Suh SW, Wiggins AK, Huang EJ, Swanson RA.
Direct phosphorylation and regulation of poly(ADP-ribose)
polymerase-1 by extracellular signal-regulated kinases 1/2. Proc
Natl Acad Sci U S A. 2006 May 2;103(18):7136-41.
CC, Kauppinen TM,
Valls AV, Swanson RA.
Minocycline inhibits poly(ADP-ribose) polymerase-1 at
nanomolar concentrations. Proc Natl Acad Sci U S A. 2006 Jun
TM, Swanson RA. The role of Glia in Excitotoxicity and Stroke.
In: Chan PH (eds) Handbook of Neurochemistry, 3rd
Edition. In press.
Swanson RA. The role of poly(ADP-ribose)polymerase-1 in CNS disease.
Neuroscience. Review. In press.