Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Yi-Jheng Peng ◽  
Junhua Geng ◽  
Ying Wu ◽  
Cristian Pinales ◽  
Jennifer Langen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Phosphatase Activity ◽  
Neuronal Activity ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Functional Domain ◽  
Multiple Modes ◽  
Disease Mutation ◽  
Activity Dependent

Neurons use multiple modes of endocytosis, including clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE), during mild and intense neuronal activity, respectively, to maintain stable neurotransmission. While molecular players modulating CME are well characterized, factors regulating ADBE and mechanisms coordinating CME and ADBE activations remain poorly understood. Here we report that Minibrain/DYRK1A (Mnb), a kinase mutated in autism and up-regulated in Down’s syndrome, plays a novel role in suppressing ADBE. We demonstrate that Mnb, together with calcineurin, delicately coordinates CME and ADBE by controlling the phosphoinositol phosphatase activity of synaptojanin (Synj) during varying synaptic demands. Functional domain analyses reveal that Synj’s 5′-phosphoinositol phosphatase activity suppresses ADBE, while SAC1 activity is required for efficient ADBE. Consequently, Parkinson’s disease mutation in Synj’s SAC1 domain impairs ADBE. These data identify Mnb and Synj as novel regulators of ADBE and further indicate that CME and ADBE are differentially governed by Synj’s dual phosphatase domains.

Down's syndrome and Parkinson's disease

Neurology ◽  
1994 ◽  
Vol 44 (12) ◽  
pp. 2419-2419 ◽  
Author(s):  
J. P. Brandel ◽  
R. Marconi ◽  
M. Serdaru ◽  
M. Vidailhet ◽  
Y. Agid
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Down's Syndrome ◽  
Down’S Syndrome

scholarly journals Down's syndrome and Parkinson's disease.

1997 ◽  
Vol 62 (3) ◽  
pp. 289-289 ◽  
Author(s):  
A Hestnes ◽  
S E Daniel ◽  
A J Lees ◽  
A Brun
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Down's Syndrome ◽  
Down’S Syndrome

scholarly journals Cholinergic Receptors in Cognitive Disorders

1986 ◽  
Vol 13 (S4) ◽  
pp. 521-527 ◽  
Author(s):  
E.K. Perry ◽  
R.H. Perry ◽  
C.J. Smith ◽  
D. Purohit ◽  
J. Bonham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Nicotinic Receptor ◽  
Down's Syndrome ◽  
Substantial Reduction ◽  
Cognitive Disorders ◽  
Down’S Syndrome ◽  
Cholinergic Receptors

Abstract:Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.

scholarly journals Detection of Lewy Bodies in Trisomy 21 (Down's Syndrome)

1993 ◽  
Vol 20 (1) ◽  
pp. 48-51 ◽  
Author(s):  
Ravi Raghavan ◽  
Clare Khin-Nu ◽  
Andrew Brown ◽  
Dorothy Irving ◽  
Paul G. Ince ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Trisomy 21 ◽  
Down's Syndrome ◽  
Lewy Bodies ◽  
Down’S Syndrome ◽  
Alzheimer Type

ABSTRACT:The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropatho-logical diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a cliniconeuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neu-rohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

SPECT-Befunde bei Hemiparkinson-Syndrom mit 99mTc-HMPAO

1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Neuronal Activity ◽  
Tracer Uptake ◽  
The Body ◽  
99Mtc Hmpao ◽  
Do So

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.

scholarly journals α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer Dagra ◽  
Douglas R. Miller ◽  
Min Lin ◽  
Adithya Gopinath ◽  
Fatemeh Shaerzadeh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Activity ◽  
Dopaminergic Neurons ◽  
Prolonged Exposure ◽  
D2 Receptor ◽  
Neuronal Firing ◽  
Dopamine Neurons ◽  
Loss Of Function ◽  
Therapeutic Implications

AbstractPathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson’s disease. The presence of aberrant intracellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of α-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by α-synuclein overexpression. These studies demonstrate that α-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson’s disease progression with significant therapeutic implications.

Altered somatosensory cortex neuronal activity in a rat model of Parkinson's disease and levodopa-induced dyskinesias

2017 ◽  
Vol 294 ◽  
pp. 19-31 ◽  
Author(s):  
Mesbah Alam ◽  
Regina Rumpel ◽  
Xingxing Jin ◽  
Christof von Wrangel ◽  
Sarah K. Tschirner ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Rat Model
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