10 A niversary of IIMCB

Publications in 2008
• Bojarski L, Pomorski P, Szybinska A, Drab M, Skibinska-
Kijek A, Gruszczynska-Biegala J, Kuznicki J. Presenilindependent
expressions of STIM proteins and dysregulation
of capacitative Ca(2+) entry in familial Alzheimer’s disease.
Biochim Biophys Acta MCR, 2008 Dec 6; [Epub ahead of
print]
• Klejman ME, Gruszczynska-Biegala J, Skibinska-Kijek
A, Wisniewska MB, Misztal K, Blazejczyk M, Bojarski L,
Kuznicki J. Expression of STIM1 in brain and puncta-like
colocalization of STIM1 and ORAI1 upon depletion of Ca 2+
store in neurons. Neurochem Int, 2009; 54:49-55
• Erickson RP, Larson-Thome K, Weberg L, Szybinska
A, Mossakowska M, Styczynska M, Barcikowska M,
Kuznicki J. Variation in NPC1, the gene encoding
Niemann-Pick C1, a protein involved in intracellular
cholesterol transport, is associated with Alzheimer disease
and/or aging in the Polish population. Neurosci Lett, 2008;
447:153–157
• Winiarska M, Bil J, Wilczek E, Wilczynski GM, Lekka M,
Engelberts PJ, Mackus WJ, Gorska E, Bojarski L, Stoklosa
T, Nowis D, Kurzaj Z, Makowski M, Glodkowska E, Issat T,
Mrowka P, Lasek W, Dabrowska-Iwanicka A, Basak GW,
Wasik M, Warzocha K, Sinski M, Gaciong Z, Jakobisiak M,
Parren PW, Golab J. Statins impair antitumor effects of
rituximab by inducing conformational changes of CD20.
PLoS Med, 2008; 5:e64
• Mossakowska M, Barcikowska M, Broczek K, Grodzicki
T, Klich-Raczka A, Kupisz-Urbanska M, Podsiadly-
Moczydlowska T, Sikora E, Szybinska A, Wieczorkowska-
Tobis K, Zyczkowska J, Kuznicki J. Polish Centenarians
Programme - Multidisciplinary studies of successful
ageing: Aims, methods, and preliminary results. Exp
Gerontol, 2008; 43:238-244
• Bojarski L, Herms J, Kuznicki J. Calcium dysregulation in
Alzheimer’s disease. Neurochem Int, 2008; 52:621-633
• Wojda U, Salinska E, Kuznicki J. Calcium ions in neuronal
degeneration. IUBMB Life, 2008; 60:575-590
• Sbroggiò M, Ferretti R, Percivalle E, Gutkowska M,
Zylicz A, Michowski W, Kuznicki J, Accornero F, Pacchioni
B, Lanfranchi G, Hamm J, Turco E, Silengo L, Tarone G,
Brancaccio M. The mammalian CHORD-containing protein
melusin is a stress response protein interacting with Hsp90
and Sgt1. FEBS Lett, 2008; 582:1788-94
• Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R,
Sinforiani E, Olivari L, Barcikowska M, Styczynska M,
Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D.
Conformationally altered p53: a novel Alzheimer’s disease
marker? Mol Psychiatry, 2008; 13:641-647
• Zabka M, Lesniak W, Prus W, Kuznicki J, Filipek A. Sgt1
has co-chaperone properties and is up-regulated by heat
shock. Biochem Biophys Res Commun, 2008; 370:179-183
• Filipek A, Michowski W, Kuznicki J. Involvement of
S100A6 (calcyclin) and its binding partners in intracellular
signaling pathways. Advan Enzyme Regul, 2008;
48:225-239
• Blazejczyk M, Wojda U. Factfile: Calmyrin 1 (review).
Calcium Binding Proteins, 2008; 3:1-3
Current Projects
We are interested in molecular mechanisms involved
in learning and memory, as well as neurodegeneration;
we study these processes at the genomic, proteomic and
cellular levels.
Our major projects are:
1. Search for bio-markers and potential therapeutic targets
for Alzheimer’s disease (AD).
2. Analysis of proteins involved in Ca 2+ homeostasis in
neurons and non-neuronal cells.
3. Analysis of Ca 2+ -binding proteins calmyrin1 and calmyrin2
in neurons.
4. Regulation and role of β-catenin/Lef1 complex in mature
neurons.
5. Characterization of biological functions of CHORD
containing proteins in the nervous system.
6. Studies on the cyclin-dependent kinase 5 involvement in
pathogenesis of Alzheimer’s disease.
1. Search for functional bio-markers and potential
therapeutic targets of Alzheimer’s disease (Emilia
Białopiotrowicz, Łukasz Bojarski, Mirosław Drab, Aleksandra
Szybińska, Bożena Kuźniewska, Urszula Wojda, in
collaboration with other laboratories)
In this area, several projects were carried out:
1.1. In cooperation with Prof. Maurizio Memo and Dr. Daniela
Uberti (University of Brescia) the conformational mutant p53
as a new putative marker to discriminate AD from non-AD
patients was analyzed. Conformation of p53 protein was
studied in cell lysates from our immortalized B lymphocytes
from 13 sporadic AD (SAD) and 10 familial AD (FAD) patients
and 12 control subjects by immunoprecipitation experiments.
Cells from SAD and FAD patients specifically expressed
an increased amount of conformationally altered p53 that
makes them distinguishable from cells of age-matched
non-AD subjects. This suggests a role for a dearrangement
of protein controlling the cell cycle in AD pathogenesis
(C. Lanni, et al., Mol Psych, 2008). Since p53 conformational
tertiary structure is influenced by redox status of the cells,
we also evaluated the oxidative profile of these patients. We
found that among the markers of oxidative stress, hydroxytransnonenal-modified
proteins were significantly increased
in FAD patients. Furthermore it is interested to note that,
besides increased levels of oxidative markers, the antioxidant
defence mechanisms were compromised in these patients.
These results supported and enhanced the first evidences of
peripheral unfolded p53 associated with AD pathology and
highlighted the identification of oxidative stress markers in
peripheral, immortalised cells derived from FAD patients.
1.2. It has been suggested that the aberrant expression
of cell cycle molecules in the brain contributes to the
development of Alzheimer’s disease (AD) and causes
neuronal death. The aim of the current study was to
determine whether the alterations in cell cycle progression
can be observed in lymphocytes from SAD and FAD
patients. Immortalized B-lymphocytes from 17 SAD and 6
FAD patients (bearing distinct PS1 mutations) were studied
in comparison to lymphocytes from 18 healthy individuals.
Laboratory of Neurodegeneration 41