Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity-dependent neuroprotective protein (ADNP) and the homologous protein ADNP2 provide cell protection. ADNP is essential for brain formation, proper brain development and neuronal plasticity, all reported to be impaired in the schizophrenia patient brains. Furthermore, reduction in ADNP expression affects social interactions, a major hallmark of schizophrenia. To evaluate a possible involvement of ADNP and ADNP2 in the pathophysiology of schizophrenia in humans, we measured relative brain mRNA transcripts of both proteins compared with control subjects. Quantitative real time polymerase chain reaction in postmortem hippocampal specimens from normal control subjects exhibited a significant ADNP to ADNP2 transcript level correlation (r=0.931, p<0.001), also apparent in a neuroglial model system. In contrast, in the hippocampus of matched schizophrenia patients, this correlation (r=0.637, p=0.014) was drastically decreased in a statistically significant manner (p=0.03), mirroring disease-associated increased ADNP2 transcripts. In the prefrontal cortex of schizophrenia patients the correlation between ADNP and ADNP2 mRNA levels was apparently higher than in the hippocampus (r=0.854, p<0.001), but did not reach a significant difference (p=0.25). Thus, imbalance in ADNP/ADNP2 expression in the brain may impact disease progression in schizophrenia.
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PMID:Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia. 2059 62

NAP (davunetide) is an active fragment of activity-dependent neuroprotective protein (ADNP). ADNP and the homologous protein ADNP2 provide cell protection. ADNP is essential for brain formation, proper development and neuronal plasticity, all reported to be impaired in schizophrenia. ADNP haploinsufficiecy inhibits social and cognitive functions, major hallmarks in schizophrenia. Imbalance in ADNP/ADNP2 expression in the schizophrenia brain may impact disease progression. NAP treatment partly ameliorates ADNP haploinsufficiecy. The microtubule, stable tubule-only polypeptide (STOP)-deficient mice were shown to provide a reliable model for schizophrenia. Daily intranasal NAP treatment significantly decreased hyperactivity in STOP-deficient mice and protected visual memory, supporting further clinical development.
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PMID:Microtubules, schizophrenia and cognitive behavior: preclinical development of davunetide (NAP) as a peptide-drug candidate. 2105 Aug 75

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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PMID:Autophagy has a key role in the pathophysiology of schizophrenia. 2436 67