Novel Pharmacotherapies for L-DOPA-Induced Dyskinesia

Tizabi, Yousef; Getachew, Bruk; Copeland, Robert L.; Moratalla, Rosario; Patricio, Felipe; Limón, Ilhuicamina Daniel; Bel, Elaine Del; Aschner, Michael

doi:10.1007/978-3-030-71519-9_218-1

Cited by 5 publications

(9 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is now evident that basal ganglia’s normal function depends on the equilibrium between the striatal cholinergic and midbrain dopaminergic systems [ 183 , 184 , 185 ]. Acetylcholine (ACh), via interaction with nicotinic receptors, regulates striatal DA release [ 25 , 154 ].…”

Section: Nicotine For Pdmentioning

confidence: 99%

“…However, no apparent benefit was noted with such a mode of nicotine administration [ 208 ]. This lack of response to nicotine patches was likely due to the steady release of nicotine and prolonged nicotinic receptor desensitization [ 3 , 185 ]. Although a nicotine patch, by maintaining a steady plasma concentration of nicotine, may be an effective intervention for smoking cessation as the desensitization of the central nicotinic receptors in critical brain reward circuitry may help ameliorate the withdrawal effects of nicotine, it is unlikely to be therapeutically efficacious for PD.…”

Section: Mode Of Nicotine Administration As a Critical Factor In Pdmentioning

confidence: 99%

“…It is also of utmost importance to distinguish between pure nicotine and nicotine derived from burning tobacco leaves, where the latter contains xenobiotics, including carcinogens and other toxins. Moreover, nicotine by itself may not only be effective in ameliorating PD symptoms and retard the progression of the disease but may also counter L-dopa-induced dyskinesia [ 3 , 185 ].…”

Section: Mode Of Nicotine Administration As a Critical Factor In Pdmentioning

confidence: 99%

See 2 more Smart Citations

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Cells

Self Cite

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.

show abstract

Section: Nicotine For Pdmentioning

confidence: 99%

Section: Mode Of Nicotine Administration As a Critical Factor In Pdmentioning

confidence: 99%

Section: Mode Of Nicotine Administration As a Critical Factor In Pdmentioning

confidence: 99%

See 1 more Smart Citation

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Soares,

Costa,

Ferrolho

et al. 2024

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Neuronal nicotinic receptors are primarily alph4-beta2 or homomeric alpha7 subtypes. Extensive research on these receptors has led to the suggestion of therapeutic potential for selective nicotinic receptor agonists in various neuropsychiatric and neurodegenerative disorders, including PD, AD, schizophrenia, depression, pain as well as smoking cessation [11][12][13].…”

Section: Nicotinic Acetylcholine Receptors (Nachrs)mentioning

confidence: 99%

Central Nicotinic and Muscarinic Receptors in Health and Disease

Tizabi¹,

Getachew²,

Tsytsarev³

et al. 2023

Acetylcholine - Recent Advances and New Perspectives

Self Cite

View full text Add to dashboard Cite

Without acetylcholine (ACh) no skeletal muscle contraction, no preganglionic sympathetic or parasympathetic activity can be obtained. This can result in dysregulation of cardiac, respiratory, gastrointestinal, and renal functions as well as disruption of fluid secretion from various glands such as tears, saliva, digestive juices, sweat, and milk. Importantly, ACh deficiency in the brain can have severe cognitive consequences. The action of ACh is mediated by two distinct classes of receptors, namely the muscarinic (mAChRs), which are G-protein coupled (metabotropic) receptors and nicotinic receptors (nAChRs), which are ligand-gated ion channels (ionotropic receptors). The focus of this chapter is on interaction of these two distinct receptor classes and its implication in health and disease. Thus, following a brief description of ACh actions and its central circuitry, an update on mAChRs and nAChRs and how their interaction may impact neuropsychiatric/neurodegenerative diseases will be provided. Moreover, potential novel therapeutic intervention based on these interactions, particularly in relationship to Alzheimer’s and Parkinson’s diseases will be touched upon.

show abstract

“…Nonetheless, the search for slowing or stopping the progression of PD is an ongoing challenge as its etiology remains elusive. The most common treatment of PD consists of dopamine replacement (e.g., levodopa = L-DOPA), which not only loses its full efficacy in a few years but may also induce severe dyskinesia ( Picconi et al 2017 ; Tizabi et al 2021b ). Hence additional studies on etiology as well as development of more efficacious interventions aiming at neuroprotection are urgently needed ( Tizabi et al 2021a ).…”

Section: Introductionmentioning

confidence: 99%

Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases

Tizabi,

Getachew,

Aschner

2023

Preprint

Self Cite

View full text Add to dashboard Cite

Toxic exposures to heavy metals, such as iron (Fe) and manganese (Mn), can result in long-range neurological diseases and are therefore of significant environmental and medical concerns. We have previously reported that damage to neuroblastoma-derived dopaminergic cells (SH-SY5Y) by both Fe and Mn could be prevented by pre-treatment with nicotine. Moreover, butyrate, a short chain fatty acid (SCFA) provided protection against salsolinol, a selective dopaminergic toxin, in the same cell line. Here, we broadened the investigation to determine whether butyrate might also protect against Fe and/or Mn, and whether, if combined with nicotine, an additive or synergistic effect might be observed. Both butyrate and nicotine concentration-dependently blocked Fe and Mn toxicities. The ineffective concentrations of nicotine and butyrate, when combined, provided full protection against both Fe and Mn. Moreover, the effects of nicotine but not butyrate could be blocked by mecamylamine, a non-selective nicotinic antagonist. On the other hand, the effects of butyrate, but not nicotine, could be blocked by beta-hydroxy butyrate, a fatty acid-3 receptor antagonist. These results not only provide further support for neuroprotective effects of both nicotine and butyrate but indicate distinct mechanisms of action for each one. Furthermore, potential utility of the combination of butyrate and nicotine against heavy metal toxicities is suggested.

show abstract

Novel Pharmacotherapies for L-DOPA-Induced Dyskinesia

Cited by 5 publications

References 93 publications

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Central Nicotinic and Muscarinic Receptors in Health and Disease

Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases

Contact Info

Product

Resources

About