Postmortem Studies of Fetal Grafts in Parkinson’s Disease: What Lessons Have We Learned?

Neural transplantation is a potential therapeutic method for Parkinson’s disease (PD). Fetal dopaminergic (DA) neurons have been important transplantation cell sources in the history of replacement therapy for PD. Several decades of preclinical animal experiments and clinical trials using fetal DA neuron transplantation in PD therapy have shown not only promising results but also problems. In order to reveal possible factors influencing the clinical outcomes, we reviewed fetal DA neuron transplantation therapies from 1970s to present, with a special focus on postmortem studies. Firstly, we gave a general description of the clinical outcomes and neuroanatomy of grafted cases; secondly, we summarized the main available postmortem studies, including the cell survival, reinnervation, and pathology development. In the end, we further discussed the link between function and structure of the grafts, seeking for the possible factors contributing to a functional graft. With our review, we hope to provide references for future transplantation trials from a histological point of view.

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Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era

Genes ◽

10.3390/genes12030430 ◽

2021 ◽

Vol 12 (3) ◽

pp. 430

Author(s):

Steven R. Bentley ◽

Ilaria Guella ◽

Holly E. Sherman ◽

Hannah M. Neuendorf ◽

Alex M. Sykes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Rare Variants ◽

Strong Family History ◽

Disease Mutations ◽

Whole Exome ◽

History Of ◽

Functional Consequences ◽

Multiplex Families

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.

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Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽

10.3390/immuno1020006 ◽

2021 ◽

Vol 1 (2) ◽

pp. 78-90

Author(s):

Johannes Burtscher ◽

Grégoire P. Millet

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Current Knowledge ◽

Cell Types ◽

Brain Cell ◽

Special Focus ◽

Molecular Alterations ◽

Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

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Natural history of lung function over one year in patients with Parkinson's disease

Respiratory Medicine ◽

10.1016/j.rmed.2021.106396 ◽

2021 ◽

Vol 182 ◽

pp. 106396

Author(s):

David A. Kaminsky ◽

Donald G. Grosset ◽

Deena M. Kegler-Ebo ◽

Salvador Cangiamilla ◽

Michael Klingler ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lung Function ◽

Natural History ◽

History Of ◽

One Year

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Stigma Experienced by Parkinson’s Disease Patients: A Descriptive Review of Qualitative Studies

Parkinson s Disease ◽

10.1155/2017/7203259 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 15

Author(s):

Marina Maffoni ◽

Anna Giardini ◽

Antonia Pierobon ◽

Davide Ferrazzoli ◽

Giuseppe Frazzitta

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Literature Review ◽

Subjective Experience ◽

Negative Impact ◽

Social Stigma ◽

Subjective Symptom ◽

Point Of View ◽

Pubmed Database ◽

Related Quality

Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor and nonmotor symptoms. Both of them imply a negative impact on Health-Related Quality of Life. A significant one is the stigma experienced by the parkinsonian patients and their caregivers. Moreover, stigma may affect everyday life and patient’s subjective and relational perception and it may lead to frustration and isolation. Aim of the present work is to qualitatively describe the stigma of PD patients stemming from literature review, in order to catch the subjective experience and the meaning of the stigma construct. Literature review was performed on PubMed database and Google Scholar (keywords: Parkinson Disease, qualitative, stigma, social problem, isolation, discrimination) and was restricted to qualitative data: 14 articles were identified to be suitable to the aim of the present overview. Results are divided into four core constructs: stigma arising from symptoms, stigma linked to relational and communication problems, social stigma arising from sharing perceptions, and caregiver’s stigma. The principal relations to these constructs are deeply analyzed and described subjectively through patients’ and caregiver’s point of view. The qualitative research may allow a better understanding of a subjective symptom such as stigma in parkinsonian patients from an intercultural and a social point of view.

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Real world clinical outcomes using a novel directional lead from a multicenter registry of deep brain stimulation for Parkinson's Disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.198 ◽

2020 ◽

Vol 79 ◽

pp. e50

Author(s):

G. Deuschl ◽

R. Jain ◽

J. Wang ◽

S. Paschen ◽

M.T. Barbe ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Clinical Outcomes ◽

Brain Stimulation ◽

Real World ◽

Multicenter Registry ◽

Deep Brain

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Respiratory disorders of Parkinson's Disease

Journal of Neurophysiology ◽

10.1152/jn.00363.2021 ◽

2021 ◽

Author(s):

Yasmin C Aquino ◽

Lais M Cabral ◽

Nicole C Miranda ◽

Monique C Naccarato ◽

Barbara Falquetto ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sleep Disturbances ◽

Respiratory Control ◽

Muscle Rigidity ◽

Upper Airways ◽

Respiratory Disorders ◽

Functional Deficits ◽

History Of ◽

Subject Making

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, mainly affecting people over 60 years of age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia and postural instability) and nonclassical symptoms (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances and respiratory disorders). Thus, patients with PD can have a significantly impaired quality of life, especially when they do not have multi-modality therapeutic follow-up. The respiratory alterations associated with this syndrome are the main cause of mortality in PD. They can be classified as peripheral when caused by disorders of the upper airways or muscles involved in breathing and as central when triggered by functional deficits of important neurons located in the brainstem and involved in respiratory control. Currently, there is little research describing these disorders, and therefore, there is no well-established knowledge about the subject, making the treatment of patients with respiratory symptoms difficult. In this review, the history of the pathology and data about the respiratory changes in PD obtained thus far will be addressed.

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