Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson's Disease. 2021

Kathleen Carmichael, and Rebekah C Evans, and Elena Lopez, and Lixin Sun, and Mantosh Kumar, and Jinhui Ding, and Zayd M Khaliq, and Huaibin Cai
Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States.

Dopamine is an important chemical messenger in the brain, which modulates movement, reward, motivation, and memory. Different populations of neurons can produce and release dopamine in the brain and regulate different behaviors. Here we focus our discussion on a small but distinct group of dopamine-producing neurons, which display the most profound loss in the ventral substantia nigra pas compacta of patients with Parkinson's disease. This group of dopaminergic neurons can be readily identified by a selective expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and accounts for 70% of total nigrostriatal dopaminergic neurons in both human and mouse brains. Recently, we presented the first whole-brain circuit map of these ALDH1A1-positive dopaminergic neurons and reveal an essential physiological function of these neurons in regulating the vigor of movement during the acquisition of motor skills. In this review, we first summarize previous findings of ALDH1A1-positive nigrostriatal dopaminergic neurons and their connectivity and functionality, and then provide perspectives on how the activity of ALDH1A1-positive nigrostriatal dopaminergic neurons is regulated through integrating diverse presynaptic inputs and its implications for potential Parkinson's disease treatment.

UI MeSH Term Description Entries
D010300 Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080924 Aldehyde Dehydrogenase 1 Family A subfamily of the aldehyde dehydrogenase family of enzymes involved in the synthesis of acetate from ethanol. ALDH1 Enzyme,Acetaldehyde Dehydrogenase 1,Aldehyde Dehydrogenase 1
D000444 Aldehyde Dehydrogenase An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70. D-Glucuronolactone Dehydrogenase,Aldehyde Dehydrogenase (NAD(+)),Aldehyde Dehydrogenase E1,Aldehyde Dehydrogenase E2,Aldehyde-NAD Oxidoreductase,Aldehyde NAD Oxidoreductase,D Glucuronolactone Dehydrogenase,Dehydrogenase, Aldehyde,Dehydrogenase, D-Glucuronolactone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras
D050697 Retinal Dehydrogenase A metalloflavoprotein enzyme involved the metabolism of VITAMIN A, this enzyme catalyzes the oxidation of RETINAL to RETINOIC ACID, using both NAD+ and FAD coenzymes. It also acts on both the 11-trans- and 13-cis-forms of RETINAL. Retinaldehyde Dehydrogenase,Cytosolic Retinal Dehydrogenase,Dehydrogenase, Cytosolic Retinal,Dehydrogenase, Retinal,Dehydrogenase, Retinaldehyde,Retinal Dehydrogenase, Cytosolic
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059290 Dopaminergic Neurons Neurons whose primary neurotransmitter is DOPAMINE. Dopamine Neurons,Dopamine Neuron,Dopaminergic Neuron,Neuron, Dopamine,Neuron, Dopaminergic,Neurons, Dopamine,Neurons, Dopaminergic

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