Journal
MOLECULAR PSYCHIATRY
Volume 20, Issue 1, Pages 126-132Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2013.174
Keywords
activity-dependent neuroprotective protein; beclin; microtubule-associated protein 1 light chain 3; BcL2; schizophrenia
Funding
- AMN Foundation
- CFTAU Montreal Circle of Friends
- Adams Super Center for Brain Studies at Tel Aviv University
- Allon Therapeutics Inc.
- Florey Institute for Neuroscience and Mental Health
- Alfred
- Victorian Forensic Institute of Medicine, and The University of Melbourne
- Australia's National Health & Medical Research Council
- Victorian Government's Operational Infrastructure Support Program
- Helen Macpherson Smith Trust
- Parkinson's Victoria
- Oberfeld
- Adams families
- Perpetual Philanthropic Services
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Autophagy is a process preserving the balance between synthesis, degradation and recycling of cellular components and is therefore essential for neuronal survival and function. Several key proteins govern the autophagy pathway including beclin1 and microtubule associated protein 1 light chain 3 (LC3). Here, we show a brain-specific reduction in beclin1 expression in postmortem hippocampus of schizophrenia patients, not detected in peripheral lymphocytes. This is in contrast with activity-dependent neuroprotective protein (ADNP) and ADNP2, which we have previously found to be deregulated in postmortem hippocampal samples from schizophrenia patients, but that now showed a significantly increased expression in lymphocytes from related patients, similar to increases in the anti-apoptotic, beclin1-interacting, Bcl2. The increase in ADNP was associated with the initial stages of the disease, possibly reflecting a compensatory effect. The increase in ADNP2 might be a consequence of neuroleptic treatment, as seen in rats subjected to clozapine treatment. ADNP haploinsufficiency in mice, which results in age-related neuronal death, cognitive and social dysfunction, exhibited reduced hippocampal beclin1 and increased Bcl2 expression (mimicking schizophrenia and normal human aging). At the protein level, ADNP co-immunoprecipitated with LC3B suggesting a direct association with the autophagy process and paving the path to novel targets for drug design.
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