Parkinsonism and Related Disorders 20S1 (2014) S68–S72 Contents lists available at SciVerse ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis Aldehyde dehydrogenase 2 in sporadic Parkinson’s disease Tanja Maria Michel a , Ludwig K¨ asbauer b , Wieland Gsell b , Julia Jecel c , Abigail Jane Sheldrick a , Miriam Cortese d , Thomas Nickl-Jockschat a , Edna Gr ¨ unblatt e,f , Peter Riederer b,g, * a Department of Psychiatry and Psychotherapy, Rostock University Medical School, Rostock, Germany b University Hospital Wuerzburg, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Wuerzburg, Germany c Department of Neurology, Danube Hospital, Center for Social Medicine East, Vienna, Austria d RWTH Laboratory for Plastic Surgery, RWTH Aachen University, Aachen, Germany e University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland f Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland g Visiting Researcher at Department of Cognitive Brain Sciences, NCGG, Aichi, Japan article info Keywords: Aldehyde dehydrogenase 2 Parkinson’s disease Mitochondrial defect Oxidative stress Aldehyde toxicity summary Aldehyde dehydrogenases (ALDH) play a key role in neuronal protection. They exert this function by metabolizing biogenic amine-related aldehydes, e.g. 3,4-dihydroxyphenylacetaldehyde (DOPAL), and by protecting neurons against aldehyde- and oxidative stress-related neurotoxicity. The role of these different isoenzymes has been discussed in other neurodegenerative disorders before. It is somewhat surprising that only few studies have investigated their role in the aetiology of Parkinson’s disease (PD), in both the degeneration of dopaminergic neurons and the formation of Lewy bodies. Earlier studies report severe alterations of the cytosolic isoform of ALDH expression (ALDH 1A1) in the substantia nigra of patients with PD. However, there are no data regarding the activity of ALDH 2 located at the inner mitochondrial membrane. Since mitochondrial dysfunctions are hypothesized to be of importance in the aetiology of PD we have examined the enzymatic activity of mitochondrial ALDH 2 in post-mortem putamen and frontal cortex of patients with PD and controls. We found that mitochondrial ALDH 2 activity in contrast to the frontal cortex was significantly increased in the putamen of patients with PD compared to controls. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction Idiopathic Parkinson’s disease (PD) is a common neurodegenerative disorder characterised by a selective degeneration of neuromelanin- containing dopaminergic (DA) neurons in the pars compacta of the substantia nigra (SNpc) projecting to the putamen and the caudate nucleus of the brain. However, the process that leads to neurodegeneration in PD remains largely unknown. Evidence suggests that both environmental factors and genetic factors on the basis of e.g. mitochondrial dysfunctions, oxidative stress (OS) and aldehyde-related toxicity are major components accounting for the specific pathophysiology of PD [1]. OS propagates cell death by increased production of free radicals, which can be either reactive oxygen species (ROS) or reactive aldehyde species (RAS). A large number of studies suggest increased OS levels in patients with PD mediated by mitochondrial dysfunction, decreased concentrations of antioxidants and elevated iron levels [2]. These processes contribute to cell degeneration via lipid peroxidation. Oxidative *Corresponding author. Prof. Dr. Dr. hc. Peter Riederer, University Hospital Wuerzburg, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, F¨ uchsleinstraße 15, 97080 Wuerzburg, Germany. E-mail address: peter.riederer@mail.uni-wuerzburg.de (P. Riederer). deamination leads to the production of aldehydes which may render toxic if aldehyde dehydroxygenase (ALDH) activity is reduced. In fact, 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) have been found to be significantly increased in post-mortem SN of Parkinson’s disease. Both types of free radicals, namely ROS and RAS, can lead to cellular damage via the modification of proteins and inhibiting enzymes [3,4]. A significant increase of 4-HNE and MDA suggests that such aldehydes are not or insufficiently metabolised into acids by ALDH. ALDH isoenzymes differ in their affinity to various aldehydes and show an organ-specific distribution [5]. There are in particular two ALDH isoenzymes which play a role in detoxifying aldehydes in the brain, namely ALDH 1A1 and ALDH 2. ALDH 1A1 is located at the cytosolic site. Therefore it is in close vicinity to monoamine oxidase (MAO). ALDH 2 is located at the inner mitochondrial membrane. This demonstrates the importance of getting rid of toxic aldehydes both within the mitochondria as well as in the cytosol [6]. There is ample evidence that in PD MAO expression and function in the SN is not disturbed, while ALDH 1A1 is significantly reduced or even not present [1,7]. In fact, an increased ratio of 3,4-dihydroxyphenylacetaldehyde (DOPAL) to 3,4-dihydroxyphenyl- acetic acid (DOPAC) in the putamen of PD suggests decreased 1353-8020/$ – see front matter © 2013 Elsevier Ltd. All rights reserved.