Author Proof 871 Review ISSN 1752-0363 10.2217/BMM.10.111 © 2010 Future Medicine Ltd Biomarkers Med. (2010) 4(6), 871–887 PeRsPective Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function Neurotrophins are a family of proteins that are essential for the development, differentiation and survival of neurons. In the 1950s, Rita Levi- Montalcini identiied the irst neurotrophin, the nerve growth-promoting factor, later renamed NGF, a molecule that could promote the growth of neurons of the sympathetic nervous system [1] . Since then, there has been signiicant evolution in the ield and other neurotrophins have been described. Today the group is composed of NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, -4, -5 and -6. All neurotrophins present similar biochemical characteristics with variable domains, which determine the bind- ing to speci ic receptors and lead to different biological effects [2] . Brain-derived neurotrophic factor is the most widely distributed neurotrophin in the CNS. A series of studies demonstrated that BDNF displays several functions, including regulation of axonal and dendritic growth and guidance, participa- tion in neurotransmitter release, and long-term potentiation [3] . Therefore, BDNF has emerged as a major regulator of synaptic plasticity. These broad functions in the CNS ascribed to BDNF make this peptide a key target in the physiopathology of several neurological and psychiatric diseases. In this article, we revise the putative role of BDNF in mood, cognitive and motor functions, and its potential use as a biomarker of neuropsychiatric disorders. Neurobiology of BDNF Human mature BDNF is a 13.5-kDa, 119-amino acid nonglycosylated polypeptide whose primary structure is conserved among humans, mice and rats. BDNF contains six cysteine residues that are believed to form three intrachain disulide link- ages. BDNF is more than 50% identical to NGF at the amino acid level. Cells known to express BDNF include neurons, astrocytes, Schwann cells, ibroblasts and, possibly, smooth muscle cells. Similar to other neurotrophins, BDNF pro- tein complex is synthesized as a precursor protein, pro-BDNF. This protein weighs approximately 28 kDa and is cleaved by a proteolytic process to the mature form of BDNF [2–4] . After transcription, pro-BDNF is wrapped and packed by the trans-Golgi system in secretory vesicles. Vesicles can be spontaneously released or more often released after stimuli [5,6] . Therefore, pro-BDNF can be secreted by neurons in dif- ferent sites of the CNS, such as the cerebral cor- tex, cerebellum, substantia nigra, amygdala and hypothamalus, or cleaved intracellularly by furin or proconvertases. Extracellular proteases such as plasmin and matrix metalloprotease-7 are also responsible for the conversion of pro-BDNF into a mature BDNF molecule [4] . Brain-derived neurotrophic factor is the most widely distributed neurotrophin in the CNS. Immunohistochemistry techniques demon- strated the presence of the protein and/or its related mRNA in cortical and hippocampal neurons. Pyramidal neurons in the primary visual cortex and other occipital areas, motor and somatosensory cortex, and insula and temporal cortex were immunoreactive to BDNF, suggest- ing that these cells are one of the most important sources of BDNF. The anatomical distribution of Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer’s disease, Huntington’s disease and Parkinson’s disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspeci ic biomarker of neuropsychiatric disorders characterized by neurodegenerative changes. KEYWORDS: Alzheimer’s disease n amyotrophic lateral sclerosis n bipolar disorder n brain-derived neurotrophic factor n depression n Huntington’s disease n Parkinson’s disease n plasma n serum Antonio Lucio Teixeira †1 , Izabela Guimarães Barbosa 1 , Breno Satler Diniz 2 & Arthur Kummer 1 1 Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Insituto de Ciências Biológicas, UFMG Avenue Antonio Carlos, 6627 – 31270-901 – Belo Horizonte, MG, Brazil 2 Laboratory of Neuroscience (LIM 27), Department and Insitute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr Ovidio Pires de Campos, 785, 05403-010 – São Paulo, Brazil † Author for correspondence: Tel.: +55 313 409 2651 altexr@gmail.com