Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

Jin, Wook

doi:10.3390/jcm9010257

Cited by 111 publications

(72 citation statements)

References 125 publications

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“…Secondly, sections containing neurons located within the oculomotor nucleus (cranial nerve III) and the substantia nigra (SN) of a male 51-year-old HC case were immunostained using the current TrkA antibody. Although oculomotor neurons also displayed TrkA immunoreactivity, SN neurons, which contain TrkB (Jin, 2020), were TrkA (Sobreviela et al, 1994) immunonegative (Supplementary Figures 1G,H). Some sections were counterstained with Gill's hematoxylin or cresyl violet for laminar identification.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Cerebellar Calcium-Binding Protein and Neurotrophin Receptor Defects in Down Syndrome and Alzheimer's Disease

Miguel

Perez

Malek‐Ahmadi

et al. 2021

Front. Aging Neurosci.

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Cerebellar hypoplasia is a major characteristic of the Down syndrome (DS) brain. However, the consequences of trisomy upon cerebellar Purkinje cells (PC) and interneurons in DS are unclear. The present study performed a quantitative and qualitative analysis of cerebellar neurons immunostained with antibodies against calbindin D-28k (Calb), parvalbumin (Parv), and calretinin (Calr), phosphorylated and non-phosphorylated intermediate neurofilaments (SMI-34 and SMI-32), and high (TrkA) and low (p75NTR) affinity nerve growth factor (NGF) receptors as well as tau and amyloid in DS (n = 12), Alzheimer's disease (AD) (n = 10), and healthy non-dementia control (HC) (n = 8) cases. Our findings revealed higher Aβ42 plaque load in DS compared to AD and HC but no differences in APP/Aβ plaque load between HC, AD, and DS. The cerebellar cortex neither displayed Aβ40 containing plaques nor pathologic phosphorylated tau in any of the cases examined. The number and optical density (OD) measurements of Calb immunoreactive (-ir) PC soma and dendrites were similar between groups, while the number of PCs positive for Parv and SMI-32 were significantly reduced in AD and DS compared to HC. By contrast, the number of SMI-34-ir PC dystrophic axonal swellings, termed torpedoes, was significantly greater in AD compared to DS. No differences in SMI-32- and Parv-ir PC OD measurements were observed between groups. Conversely, total number of Parv- (stellate/basket) and Calr (Lugaro, brush, and Golgi)-positive interneurons were significantly reduced in DS compared to AD and HC. A strong negative correlation was found between counts for Parv-ir interneurons, Calr-ir Golgi and brush cells, and Aβ42 plaque load. Number of TrkA and p75NTR positive PCs were reduced in AD compared to HC. These findings suggest that disturbances in calcium binding proteins play a critical role in cerebellar neuronal dysfunction in adults with DS.

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Section: Immunohistochemistrymentioning

confidence: 99%

Cerebellar Calcium-Binding Protein and Neurotrophin Receptor Defects in Down Syndrome and Alzheimer's Disease

Miguel

Perez

Malek‐Ahmadi

et al. 2021

Front. Aging Neurosci.

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“…Neurodegenerative protein markers associate with NDD but do not correlate to vCSF-cfmtDNA levels. To further assess the links between vCSF-cfmtDNA and neurodegeneration we compared cfmtDNA levels to the abundance of CSF protein markers of neurodegeneration 43,44 , including neuron-specific enolase (NSE) 45,46 , 14-3-3 zeta and 14-3-3 beta 47 , alpha-synuclein 48,49 and tropomyosin receptor kinase B (TRKB) 50,51 . To investigate potential associations with mitochondrial debris, extracellular and/or synaptic vesicles, vCSF-cfmtDNA was compared to the levels of the most abundant synaptic vesicle membrane protein synaptophysin [52][53][54] and mitochondrial markers: SDHA (an inner mitochondrial membrane marker) 55 , TFAM (a mitochondrial transcription factor, the expression of which often reflects mtDNA level) 56 and porin (to investigate mitochondrial mass) 57 .…”

Section: Vcsf-cfmtdna Is Increased In Patients Exhibiting Neocorticalmentioning

confidence: 99%

Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

Lowes

Kurzawa‐Akanbi

Pyle

et al. 2020

Sci Rep

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Cell-free mitochondrial DNA (cfmtDNA) is detectable in almost all human body fluids and has been associated with the onset and progression of several complex traits. In-life assessments indicate that reduced cfmtDNA is a feature of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. However, whether this feature is conserved across all neurodegenerative diseases and how it relates to the neurodegenerative processes remains unclear. In this study, we assessed the levels of ventricular cerebrospinal fluid-cfmtDNA (vCSF-cfmtDNA) in a diverse group of neurodegenerative diseases (NDDs) to determine if the in-life observations of reduced cfmtDNA seen in lumbar CSF translated to the post-mortem ventricular CSF. To investigate further, we compared vCSF-cfmtDNA levels to known protein markers of neurodegeneration, synaptic vesicles and mitochondrial integrity. Our data indicate that reduced vCSF-cfmtDNA is a feature specific to Parkinson’s and appears consistent throughout the disease course. Interestingly, we observed increased vCSF-cfmtDNA in the more neuropathologically severe NDD cases, but no association to protein markers of neurodegeneration, suggesting that vCSF-cfmtDNA release is more complex than mere cellular debris produced following neuronal death. We conclude that vCSF-cfmtDNA is reduced in PD, but not other NDDs, and appears to correlate to pathology. Although its utility as a prognostic biomarker is limited, our data indicate that higher levels of vCSF-cfmtDNA is associated with more severe clinical presentations; suggesting that it is associated with the neurodegenerative process. However, as vCSF-cfmtDNA does not appear to correlate to established indicators of neurodegeneration or indeed indicators of mitochondrial mass, further work to elucidate its exact role is needed.

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“…Clinical data show that women with low estrogen exposure can develop PD earlier than women with high estrogen exposure ( Ragonese et al, 2004 ), indicating a role for this sex hormone in PD’s pathogenesis. In that sense, estrogens also appear to have a protective role in PD progression and treatment response ( Saunders-Pullman et al, 1999 ; Shulman, 2002 ; Jin, 2020 ). Estrogens could positively affect dopamine neurotransmission by reducing the expression of catechol-O-methyltransferase (COMT), the enzyme responsible for dopamine degradation ( Jiang et al, 2003 ).…”

Section: Estrogens In Neurodegenerationmentioning

confidence: 99%

The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneficial or Harmful?

Bustamante-Barrientos

Méndez-Ruette

Ortloff

et al. 2021

Front. Cell. Neurosci.

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Estrogens and estrogen-like molecules can modify the biology of several cell types. Estrogen receptors alpha (ERα) and beta (ERβ) belong to the so-called classical family of estrogen receptors, while the G protein-coupled estrogen receptor 1 (GPER-1) represents a non-classical estrogen receptor mainly located in the plasma membrane. As estrogen receptors are ubiquitously distributed, they can modulate cell proliferation, differentiation, and survival in several tissues and organs, including the central nervous system (CNS). Estrogens can exert neuroprotective roles by acting as anti-oxidants, promoting DNA repair, inducing the expression of growth factors, and modulating cerebral blood flow. Additionally, estrogen-dependent signaling pathways are involved in regulating the balance between proliferation and differentiation of neural stem/progenitor cells (NSPCs), thus influencing neurogenic processes. Since several estrogen-based therapies are used nowadays and estrogen-like molecules, including phytoestrogens and xenoestrogens, are omnipresent in our environment, estrogen-dependent changes in cell biology and tissue homeostasis have gained attention in human health and disease. This article provides a comprehensive literature review on the current knowledge of estrogen and estrogen-like molecules and their impact on cell survival and neurodegeneration, as well as their role in NSPCs proliferation/differentiation balance and neurogenesis.

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Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease

Cited by 111 publications

References 125 publications

Cerebellar Calcium-Binding Protein and Neurotrophin Receptor Defects in Down Syndrome and Alzheimer's Disease

Cerebellar Calcium-Binding Protein and Neurotrophin Receptor Defects in Down Syndrome and Alzheimer's Disease

Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneficial or Harmful?

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