FinlandHelsinki
Institute of BiotechnologyUniversity of Helsinki Group Leader
Mart Saarma
Tel. +358-9-191 59359
E-mail: mart.saarma
-at- helsinki. fi Institute of Biotechnology
Street address: Viikinkaari 9 (P.O.Box 56)
00014 University of Helsinki
Finland
Tel: +358-9-1911
fax +358-9-1915 9366 | Our
group is interested in the structure, biology and therapeutic effects
of neurotrophic factors. We study GDNF family ligands (GDNF, neurturin,
artemin and persephin) and their receptors, GFRα1-4 and Ret, in brain
development and in disease. Our group has discovered a new neurotrophic
factor called conserved dopaminergic neurotrophic factor (CDNF) and
demonstrated that it is very efficiently protecting and repairing brain
dopaminergic neurones. We are currently studying the structure, biology
and therapeutic potential of this neurotrophic factor. | Neurotrophic
factors include i.e. neurotrophins (NGF, BDNF, NT-3, NT-4), neurokines
(e.g. CNTF), and glial cell line-derived neurotrophic factor (GDNF)
family ligands (GFLs) (Airaksinen and Saarma, 2002; Bespalov and
Saarma, 2007). Neurotrophic factors and their receptors regulate the
development and physiology of neurons, but still very little is known
about their roles in the central nervous system (CNS). Surprisingly,
neurotrophic factors from invertebrates have not been described so far.
We therefore search for the new neurotrophic factors, identify their
receptors, analyze their molecular structures and study their
biology.Glial cell line-derived neurotrophic factor (GDNF) and
neurturin (NRTN) are neurotrophic factors that support the development
and survival of peripheral neurons as well as midbrain dopamine
neurons, motoneurons and have therapeutic potential for the treatment
of neurodegenerative diseases, such as Parkinson’s disease and
amyotrophic lateral sclerosis. We have earlier discovered that RET is a
receptor for GDNF (Durbec et al., 1996; Trupp et al., 1996), later
found the NRTN receptor GFRα2 (Suvanto et al., 1997) and demonstrated
that NRTN/GFRα2 signalling is required for the development of
parasympathetic neurons (Rossi et al., 1999). Our group further showed
that GDNF regulates spermatogenesis (together with Dr. Hannu Sariola)
(Meng et al., 2000), characterized the new, mammalian persephin (PSPN)
receptor GFRα4 (Lindahl et al., 2001; Lindfors et al., 2006) and
demonstrated that soluble GFRα4 can in the absence of PSPN ligand
directly activate RET (Yang et al., 2007). We have also found that
oncogenic RET MEN2B can signal already in the ER on his way to the
plasma membrane (Runeberg-Roos et al, 2007). Interestingly, in vivo
results show that MEN2B signalling regulates the number of dopamine
neurons and up-regulates dopamine levels in the mouse brain (Mijatovic
et al., 2007). | 1. Characterization of novel neurotrophic factors and search for their receptors 2. Novel growth factors for the treatment of Parkinson’s disease 3. GFL receptors, their structure, signalling and in vivo functions |
