Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases
Abstract
:2. The System of 5-HT
2.1. Characteristics of the 5-HT System
2.2. 5-HT Receptor and Its Function
2.2.1. 5-HT1R
2.2.2. 5-HT2R
2.2.3. 5-HT3R
2.2.4. 5-HT4R
2.2.5. 5-HT5R
2.2.6. 5-HT6R
2.2.7. 5-HT7R
3. The Diagnostic and Therapeutic Potential of 5-HT in NDs
3.1. 5-HT Targeting AD Therapy
3.2. 5-HT Targeted PD Therapy
3.3. 5-HT Targeting ALS Therapy
3.4. 5-HT Targeted HD Therapy
3.5. 5-HT Targeted MS Therapy
3.6. The Potential of 5-HT as a Biomarker in Diagnosing NDs.
4. Progress of Clinical Research on Targeting 5-HT for NDs
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
5-HT | Serotonin |
PD | Parkinson’s disease |
AD | Alzheimer’s disease |
HD | Huntington’s disease |
ALS | Amyotrophic lateral sclerosis |
MS | Multiple sclerosis |
ND | Neurodegenerative disease |
CNS | central nervous system |
AChE | acetylcholinesterase |
Aβ | beta-amyloid |
SNpc | substantia nigra pars compacta |
BG | basal ganglia |
SERT | 5-HT transporters |
BDNF | brain-derived neurotrophic factor |
LID | L-DOPA-induced dyskinesia |
5-HTP | 5-hydroxytryptophan |
SSRIs | Selective serotonin reuptake inhibitors |
PDP | PD psychosis |
SDH | spinal dorsal horn |
FALS | familial ALS |
SALS | sporadic ALS |
TDP-43 | TAR DNA-binding protein 43 |
SOD1 | superoxide dismutase 1 |
NAS | N-acetyl-5-HT |
HLA | human leukocyte antigen |
5-HTTLPR | 5-HT transporter-linked polymorphic region |
ICD | Impulse control disorder |
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5-HT Receptors | Possible Functions | Known Agonist/Antagonist |
---|---|---|
5-HT1A | anxiety, mood, cognition, suicidal tendencies, appetite, sleep, and pain perception | Buspirone |
5-HT1B/1D | stress responses, mood, and motor control | Naratriptan |
Sumatriptan | ||
5-HT1F | pain | Lasmiditan |
5-HT2A | cognition, mood, perception, and behavior | Risperidone |
Olanzapine | ||
5-HT2C | appetite regulation, weight control, mood, and behavior regulation | Lorcaserin |
5-HT3 | vomiting reflex, cognition, and anxiety | Ondansetron |
Granisetron | ||
Palonosetron | ||
5-HT4 | neurotransmission, gastrointestinal motility and secretion, and memory | Cisapride |
Mosapride | ||
Tegaserod | ||
5-HT6 | memory, energy metabolism, and mood | AVN-211 |
5-HT7 | learning and memory, mood regulation, sleep, addictive behaviors, and pain | SB-269970 |
SB-656104-A |
NCT Number | Stage | ND Type | Drug | Sample Size | Object | Mechanism | Year | Locations | Status |
---|---|---|---|---|---|---|---|---|---|
NCT03652870 | III | Parkinson’s disease (PD) | Nortriptyline | 52 | Depression in PD | tricyclic antidepressants | 29-Aug-18 | Royal Free London NHS Foundation Trust, London, United Kingdom | + |
Escitalopram | selective serotonin reuptake inhibitor | ||||||||
NCT03947216 | II | Parkinson’s disease | Pimavanserin | 130 | Impulse control disorder (ICD) in PD | selective serotonin 5-HT2A inverse agonist | 13-May-19 | Service de Neurologie-CHU Besançon, Besançon, France | = |
NCT04292223 | IV | Parkinson’s disease | Pimavanserin | 29 | Parkinson’s disease psychosis | selective serotonin 5-HT2A inverse agonist | 3-Mar-20 | Movement Disorders Center of Arizona, Scottsdale, Arizona, United States | + |
NCT04373317 | IV | Parkinson’s disease | Pimavanserin | 358 | Parkinson’s disease psychosis | selective serotonin 5-HT2A inverse agonist | 4-May-20 | Southern Arizona VA Health Care System, Tucson, AZ, Tucson, Arizona, United States | = |
Quetiapine | 5-HT2A receptor antagonist | ||||||||
NCT05357612 | IV | Parkinson’s disease | Pimavanserin | 75 | measure baseline 5HT2A receptor density | selective serotonin 5-HT2A inverse agonist | 3-May-22 | Vanderbilt University Medical Center, Nashville, Tennessee, United States | = |
NCT05590637 | IV | Parkinson’s disease | Pimavanserin | 94 | Parkinson’s disease psychosis, dementia with Lewy bodies | selective serotonin 5-HT2A inverse agonist | 21-Oct-22 | UT Health Science Center—San Antonio, San Antonio, Texas, United States | = |
Quetiapine | 5-HT2A receptor antagonist | ||||||||
NCT05796167 | Early I | Parkinson’s disease | Pimavanserin | 10 | sleep quality in patients with PD and visual hallucinations/delusions | selective serotonin 5-HT2A inverse agonist | 3-Apr-23 | − | − |
NCT04167813 | II | Parkinson’s disease | Ondansetron | 306 | Parkinson’s hallucinations, dementia with Lewy bodies | 5-HT3 receptor antagonist | 19-Nov-19 | Grampian Aberdeen, United Kingdom | = |
NCT04497168 | II | Parkinson’s disease | Citalopram | 58 | reduce visuospatial cortex Aβ plaque accrual | Selective serotonin reuptake inhibitors | 4-Aug-20 | University of Michigan, Ann Arbor, Michigan, United States | = |
NCT04932434 | II | Parkinson’s disease | Psilocybin | 10 | depression and anxiety in PD | 5-HT2A receptor agonist | 21-Jun-21 | University of California, San Francisco, United States | = |
NCT05148884 | II | Parkinson’s disease | NLX-112 | 27 | L-DOPA-induced dyskinesia in PD | high-efficacy selective 5-HT1A receptor agonist | 8-Dec-21 | Sahlgrenska Hospital, Gothenburg, Sweden | + |
NCT03724942 | III | Alzheimer’s disease (AD) | Brexpiprazole | 164 | Agitation associated with dementia of the Alzheimer’s type | 5-HT1A, 5-HT2A receptor antagonists | 30-Oct-18 | Jisenkai Nanko Psychiatric Institute Shirakawa, Japan | + |
NCT04123314 | I | Alzheimer’s disease | Psilocybin | 20 | depression in mild cognitive impairment and early AD | 5-HT2A receptor agonist | 10-Oct-19 | Behavioral Pharmacology Research Unit, Baltimore, Maryland, United States | = |
NCT04341467 | − | Alzheimer’s disease | Olanzapine | 76 | Behavioral and psychological symptoms of dementia in AD | 5-HT2A receptor antagonist | 10-Apr-20 | Tianjin Anding Hospital, Tianjin, Tianjin, China | = |
NCT05282550 | II | Alzheimer’s disease | Trazodone | 100 | Amnestic mild cognitive impairment | 5-HT2A receptor antagonist | 16-Mar-22 | Johns Hopkins Hospital, Baltimore, Maryland, United States | = |
NCT05397639 | III | Alzheimer’s disease | Masupirdine | 375 | Agitation, Alzheimer’s type dementia | 5-HT6 receptor antagonist | 31-May-22 | ATP Clinical Research, Inc. Costa Mesa, California, United States | = |
NCT04071639 | I | Huntington’s disease (HD) | Risperidone | 60 | Huntington’s disease motor, MMSE, psychiatric, and functional domains | 5-HT2A receptor antagonist | 28-Aug-19 | Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China | = |
Haloperidol | 5-HT2A, 5-HT2C receptor antagonists | ||||||||
Zoloft | Selective serotonin reuptake inhibitors | ||||||||
NCT04302870 | II/III | Amyotrophic lateral sclerosis (ALS) | Trazodone | 800 | Motor neuron disease | 5-HT2A receptor antagonist | 10-Mar-20 | Southern Health and Social Care Trust, Craigavon Area Hospital, Portadown, County Armagh, United Kingdom | = |
NCT04546698 | − | Multiple sclerosis (MS) | − | 78 | 5-HT7 receptor implication in inflammatory mechanisms in MS | 5-HT7 receptor | 14-Sep-20 | CHR Orléans, Orléans, France | + |
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Xing, C.; Chen, H.; Bi, W.; Lei, T.; Hang, Z.; Du, H. Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases. Int. J. Mol. Sci. 2024, 25, 13446. https://doi.org/10.3390/ijms252413446
Xing C, Chen H, Bi W, Lei T, Hang Z, Du H. Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases. International Journal of Molecular Sciences. 2024; 25(24):13446. https://doi.org/10.3390/ijms252413446
Chicago/Turabian StyleXing, Cencan, Hongyu Chen, Wangyu Bi, Tong Lei, Zhongci Hang, and Hongwu Du. 2024. "Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases" International Journal of Molecular Sciences 25, no. 24: 13446. https://doi.org/10.3390/ijms252413446
APA StyleXing, C., Chen, H., Bi, W., Lei, T., Hang, Z., & Du, H. (2024). Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases. International Journal of Molecular Sciences, 25(24), 13446. https://doi.org/10.3390/ijms252413446