Immunotherapy for Parkinson’s disease

Schwab, Aaron; Thurston, Mackenzie J.; Machhi, Jatin; Olson, Katherine E.; Namminga, Krista L.; Gendelman, Howard E.; Mosley, R. Lee

doi:10.1016/j.nbd.2020.104760

Cited by 70 publications

(60 citation statements)

References 160 publications

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“…Unfortunately, however, the current therapies for AD, PD and depression are not fully adequate for growing treatment needs. The drugs clinically used for the treatment of AD or PD show limited efficacy with only slowing the disease progress or just alleviating symptoms [ 38 , 70 , 71 ]. Similarly, current therapies for depression exhibit a number of limitations such as delayed onset of action, insufficient efficacy, and unwanted side effects [ 72 ].…”

Section: Major Pathologies and Therapeutic Strategies Of Ad Pd Amentioning

confidence: 99%

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

Thu

Cho

2020

IJMS

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Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (Garcinia mangostana L.,) pericarp (MP) and its xanthones may provide therapeutic advantages for these disorders. In this review, we discuss potential therapeutic value of MP-derived agents in AD, PD, and depression with their pharmacokinetic and safety profiles. MP-derived agents have shown multifunctional effects including neuroprotective, antioxidant, and anti-neuroinflammatory actions. In addition, they target specific disease pathologies, such as amyloid beta production and deposition as well as cholinergic dysfunction in AD; α-synuclein aggregation in PD; and modulation of monoamine disturbance in depression. Particularly, the xanthone derivatives, including α-mangostin and γ-mangostin, exhibit potent pharmacological actions. However, low oral bioavailability and poor brain penetration may limit their therapeutic applications. These challenges can be overcome in part by administering as a form of MP extract (MPE) or using specific carrier systems. MPE and α-mangostin are generally safe and well-tolerated in animals. Furthermore, mangosteen-based products are safe for humans. Therefore, MPE and its bioactive xanthones are promising candidates for the treatment of AD, PD, and depression. Further studies including clinical trials are essential to decipher their efficacy, and pharmacokinetic and safety profiles in these disorders.

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Section: Major Pathologies and Therapeutic Strategies Of Ad Pd Amentioning

confidence: 99%

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

Thu

Cho

2020

IJMS

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“…It is also speculated that the disruption in the BBB as a result of COVID-19 associated cytokine storm syndrome may result in the progression of neurodegenerative disorder. The presence of proinflammatory mediators (IL-6 and TNFα) have been found in the CSF and the brain tissues of the deceased patients of Parkinson's disease (Schwab et al 2020). The presence of the proinflammatory mediators IL-1 and IL-6, which leads to the Aβ deposition, supports the hypothesis that the neuroinflammation due to cytokine storm may lead to Alzheimer's disease (Serrano-Castro et al 2020).…”

Section: Neurodegenerative Disordermentioning

confidence: 79%

CNS implications of COVID-19: a comprehensive review

Nagu

Parashar

Behl

et al. 2020

Reviews in the Neurosciences

104

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COVID-19 was first reported in December 2019 in the Wuhan city of China, and since then it has spread worldwide taking a heavy toll on human life and economy. COVID-19 infection is commonly associated with symptoms like coughing, fever, and shortness of breath, besides, the reports of muscle pain, anosmia, hyposmia, and loss of taste are becoming evident. Recent reports suggest the pathogenic invasion of the SARS-CoV-2 into the CNS, that could thereby result in devastating long term complications, primarily because some of these complications may go unnoticed for a long time. Evidence suggest that the virus could enter the CNS through angiotensin-converting enzyme-2 (ACE-2) receptor, neuronal transport, haematogenous route, and nasal route via olfactory bulb, cribriform plate, and propagates through trans-synaptic signalling, and shows retrograde movement into the CNS along nerve fiber. COVID-19 induces CNS inflammation and neurological degenerative damage through a diverse mechanism which includes ACE-2 receptor damage, cytokine-associated injury or cytokine storm syndrome, secondary hypoxia, demyelination, blood–brain barrier disruption, neurodegeneration, and neuroinflammation. Viral invasion into the CNS has been reported to show association with complications like Parkinsonism, Alzheimer’s disorder, meningitis, encephalopathy, anosmia, hyposmia, anxiety, depression, psychiatric symptoms, seizures, stroke, etc. This review provides a detailed discussion of the CNS pathogenesis of COVID-19. Authors conclude that the COVID-19 cannot just be considered as a disorder of the pulmonary or peripheral system, rather it has a significant CNS involvement. Therefore, CNS aspects of the COVID-19 should be monitored very closely to prevent long term CNS complications, even after the patient has recovered from COVID-19.

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“…15 Because iRBD is closely related to prodromal PD, 16 these findings support peripheral immunity as an early player in the chain of events ultimately leading to neurodegeneration, and emphasize its potential as a target for novel antiparkinson therapeutic strategies. 35 C D 4 + T -C E L L S I G N A T U R E I N i R B D A N D P D…”

Section: Discussionmentioning

confidence: 99%

CD4+ T‐cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease

Francesco

Terzaghi²,

Storelli

et al. 2020

Movement Disorders

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Background CD4+ T‐cell dysregulation occurs in Parkinson's disease (PD); however, it is unknown whether it contributes to PD development. The objective of this study was to investigate transcription factor gene expression in CD4+ T cells in idiopathic rapid eye movement sleep behavior disorder, the strongest risk factor for prodromal PD. Methods Expression of transcription factors (TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2) was measured in CD4+ T cells from 33 polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder subjects and compared with expression in cells from matched healthy subjects and antiparkinson drugs‐naive PD patients. Results Compared with healthy subjects, idiopathic rapid eye movement sleep behavior disorder subjects and PD patients had lower TBX21, STAT3, and STAT4, and higher FOXP3 expression. TBX21 expression discriminated healthy subjects from idiopathic rapid eye movement sleep behavior disorder subjects and PD patients, but not idiopathic rapid eye movement sleep behavior disorder subjects with PD. Conclusions In idiopathic rapid eye movement sleep behavior disorder subjects CD4+ T cells exhibit a peculiar molecular signature strongly resembling cells from PD patients, suggesting early involvement of peripheral immunity in PD. © 2020 International Parkinson and Movement Disorder Society

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Immunotherapy for Parkinson’s disease

Cited by 70 publications

References 160 publications

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

CNS implications of COVID-19: a comprehensive review

CD4+ T‐cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease

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