{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPDE10A is a dual‐substrate phosphodiesterase that regulates intracellular levels of both cAMP and cGMP and is highly enriched in striatal medium spiny neurons where it modulates neuronal excitability, motor output, learning and reward processing. Studies in transgenic and knockout animal models demonstrate that a loss or inhibition of PDE10A perturbs normal striatal signaling—resulting in altered locomotor activity, delayed conditioned responses, and imbalanced activation of dopaminergic pathways. In Huntington’s disease models and in human patients, early declines in PDE10A mRNA and protein precede overt motor symptoms, suggesting that decreases in PDE10A contribute to cyclic nucleotide dysregulation and downstream motor and cognitive deficits. Notably, while most reports focus on central nervous system functions, one study of demyelinating neuropathies related to mutations in myelin protein P0 underscores that phosphodiesterase‐linked signaling alterations are specific to conditions affecting striatal circuitry rather than generalized neuropathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established role in modulating corticostriatal transmission, PDE10A has been implicated in broader physiological processes. Its inhibition not only shows promise as an antipsychotic strategy by preferentially enhancing D2 receptor pathway activity and altering incentive salience attribution, but also exerts metabolic effects that reduce food intake and counteract diet-induced obesity. Moreover, evidence of PDE10A upregulation in diseased hearts links this enzyme to cardiac remodeling and dysfunction, while its inducible expression in activated macrophages points to a contributory role in pulmonary inflammation and, by extension, vascular remodeling as seen in intimal hyperplasia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent work also highlights the therapeutic potential of modulating PDE10A activity in conditions of brain injury. Pharmacological deactivation of PDE10A after ischemic stroke has been shown to boost long‐term neuronal survival, neurogenesis, angiogenesis, and axonal plasticity—underscoring PDE10A as a promising target to enhance post‐ischemic tissue remodeling and functional recovery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A L O Hebb, H A Robertson, E M Denovan-Wright "}, {"type": "b", "children": [{"type": "t", "text": "Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2003.11.009"}], "href": "https://doi.org/10.1016/j.neuroscience.2003.11.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14751289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14751289"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Judith A Siuciak, Sheryl A McCarthy, Douglas S Chapin, et al. 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