Abstract:
:Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder. A defining hallmark of the AD brain is the presence of intraneuronal neurofibrillary tangles (NFTs) which are made up of abnormally modified tau, with aberrant phosphorylation being the most studied posttranslational modification (PTM). Although the accumulation of tau as NFTs is an invariant feature of the AD brain, it has become evident that these insoluble aggregates are likely not the primary pathogenic form of tau, rather soluble forms of tau with abnormal PTMs are the mediators of toxicity. The most prevalent PTM on tau is phosphorylation, with the abnormal modification of specific residues on tau playing a key role in its toxicity. Even though it is widely accepted that tau with aberrant PTMs facilitates neurodegeneration, the precise cellular mechanisms remain unknown. Nonetheless, there is an evolving conceptual framework that an important contributing factor may be selective pathological tau species compromising mitochondrial biology. Understanding the mechanisms by which tau with site-specific PTM impacts mitochondria is crucial for understanding the role tau plays in AD. Here, we provide a brief introduction to tau and its phosphorylation and function in a physiological context, followed by a discussion of the impact of soluble phosphorylated tau species on neuronal processes in general and mitochondria more specifically. We also discuss how therapeutic strategies that attenuate pathological tau species in combination with treatments that improve mitochondrial biology could be a potential therapeutic avenue to mitigate disease progression in AD and other tauopathies.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Guha S,Johnson GVW,Nehrke Kdoi
10.1007/s12035-020-02084-0subject
Has Abstractpub_date
2020-12-01 00:00:00pages
5103-5120issue
12eissn
0893-7648issn
1559-1182pii
10.1007/s12035-020-02084-0journal_volume
57pub_type
杂志文章,评审abstract::CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its bi...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-016-9787-4
更新日期:2017-04-01 00:00:00
abstract::Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02224-6
更新日期:2020-11-27 00:00:00
abstract::Although neurons in the adult mammalian CNS are inherently incapable of regeneration after injury, we previously showed that exogenous delivery of pigment epithelium-derived factor (PEDF), a 50-kDa neurotrophic factor (NTF), promoted adult retinal ganglion cell neuroprotection and axon regeneration. Here, we show that...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1614-2
更新日期:2019-11-01 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor β superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the pr...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8443-5
更新日期:2013-12-01 00:00:00
abstract::Several plant-derived natural compounds are known to exhibit anti-amyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer's disease. The mechanisms of their anti-amyloid activity are not well known. In this regard, many natural compounds are known to exhibit direct binding to...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-015-9301-4
更新日期:2016-08-01 00:00:00
abstract::Previous studies have demonstrated depressive or hibernation-like roles of phenothiazine neuroleptics [combined chlorpromazine and promethazine (C + P)] in brain activity. This ischemic stroke study aimed to establish neuroprotection by reducing oxidative stress and improving brain metabolism with post-ischemic C + P ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0280-x
更新日期:2017-12-01 00:00:00
abstract::Maternal deprivation (MD) induces behavioral changes and impacts brain circuits that could be associated with the pathophysiology of depression. This study investigated the markers of microglia and astrocyte activation as well as indoleamine 2,3-dioxygenase (IDO) expression in developmental programming after early lif...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1161-2
更新日期:2019-02-01 00:00:00
abstract::Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients w...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-9030-0
更新日期:2016-01-01 00:00:00
abstract::Information processing in neurobiological systems is commonly thought to rely on the assessment of a signal-to-noise ratio as the key mechanism of signal detection; it assumes and requires that both signal and noise are concurrently available. An alternative theory holds that detection proceeds by the system appreciat...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:24:1-3:145
更新日期:2001-08-01 00:00:00
abstract::Olfactory dysfunction is deeply associated with quality of human life in the aging population. Olfactory dysfunction is an occasional presymptomatic sign of neuroimmunological multiple sclerosis, neuromyelitis optica, and systemic lupus erythematosus. Olfaction is initially processed by olfactory receptor cells that c...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-018-1341-0
更新日期:2019-05-01 00:00:00
abstract::Synaptic vesicle proton V-ATPase is an essential component in synaptic vesicle function. Active acidification of synaptic vesicles, triggered by the V-ATPase, is necessary for neurotransmitter storage. Independently from its proton transport activity, an additional important function of the membrane-embedded sector of...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1324-1
更新日期:2019-05-01 00:00:00
abstract::Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NS...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9225-z
更新日期:2016-05-01 00:00:00
abstract::Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) i...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0524-4
更新日期:2018-03-01 00:00:00
abstract::Parkinson's disease (PD) is a highly prevalent neurodegenerative disease for which no disease-modifying treatments are available, mainly because knowledge about its pathogenic mechanism is still incomplete. Recently, a key role for lipids emerged, but lipid profiling of brain samples from human subjects is demanding. ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01733-3
更新日期:2020-02-01 00:00:00
abstract::The decline in brain noradrenaline levels is associated with the progression of certain neurodegenerative diseases. This seems to be due, at least in part, to the ability of noradrenaline to limit glial activation and to reduce the damage associated with it. Our previous studies of the mechanisms involved in this proc...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0960-9
更新日期:2018-10-01 00:00:00
abstract::Three early signals of asymmetry have been described to occur in a single neurite of neurons at stage 2 of differentiation (before polarization) and shown to be essential for neuronal polarization: (i) accumulation of stable microtubules, (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii) polari...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0144-4
更新日期:2017-10-01 00:00:00
abstract::Findings from observational and experimental studies suggest that maternal inflammation during pregnancy is associated with autism spectrum disorder (ASD). We report the first study in humans to examine this association in a large prospective birth cohort. We studied 788 mother-child pairs from the Seychelles Child De...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1424-y
更新日期:2019-07-01 00:00:00
abstract::We have recently demonstrated that δ-opioid receptor (DOR) activation attenuates α-synuclein expression/aggregation induced by MPP(+) and/or severe hypoxia. Since α-synuclein plays a critical role in the pathogenesis of Parkinson's disease, DOR activation may trigger an antiparkinson pathway(s) against α-synuclein-ind...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1316-1
更新日期:2019-05-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease which is characterized by progressive memory loss, the accumulation of β-amyloid peptide (Aβ) (mainly Aβ1-42), and more recently, by neuroinflammation, which has been highlighted as playing a central role in the development and progress of AD. This study utilized...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1211-9
更新日期:2019-04-01 00:00:00
abstract::Parkinson's disease (PD) is one of the several neurodegenerative diseases where accumulation of aggregated proteins like α-synuclein occurs. Dysfunction in autophagy leading to this protein build-up and subsequent dopaminergic neurodegeneration may be one of the causes of PD. The mechanisms that impair autophagy remai...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1340-1
更新日期:2019-06-01 00:00:00
abstract::NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STE...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0555-x
更新日期:2018-04-01 00:00:00
abstract::Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor subtype. Despite that metastasis of GBM beyond the central nervous system (CNS) is rare, its malignancy is attributed to the highly infiltration trait, leading to the difficulty of complete surgical excision. Matrix gla protein (MGP) is a vita...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0677-1
更新日期:2018-06-01 00:00:00
abstract::Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation. However, the molecular mechanisms that trigger dendritic spine loss remain ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0349-6
更新日期:2018-01-01 00:00:00
abstract::Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been previously investigated for its neuroprotective effects in vitro and in vivo. In the present study, we aimed to evaluate its possible beneficial effects in a well-established preclinical mixed model of familial Alzheimer's disease (AD) and type...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01849-6
更新日期:2020-04-01 00:00:00
abstract::Spinal cord injury (SCI) is a traumatic event resulting in disturbances to normal sensory, motor, or autonomic functions, which ultimately impacts a patient's physical, psychological, and social well-being. Until now, no available therapy for SCI can effectively slow down or halt the disease progression. Compared to t...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-015-9157-7
更新日期:2016-07-01 00:00:00
abstract::Growing evidence has indicated that iron deposition is one of the key factors leading to neuronal death in the neurodegenerative diseases. Ferritin is a hollow iron storage protein composed of 24 subunits of two types, ferritin heavy chain (FTH) and ferritin light chain (FTL), which plays an important role in maintain...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-02277-7
更新日期:2021-01-28 00:00:00
abstract::Interleukin-1 (IL-1) has been implicated in neuroimmune responses and has pleiotropic actions in the brain. Compelling evidence has shown that IL-1 is a major mediator of inflammation and the progression of cell death in response to brain injury and cerebral ischemia. Its expression is strongly increased in these path...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:27:3:239
更新日期:2003-06-01 00:00:00
abstract::Tonic inhibition mediated by ambient levels of GABA that activate extrasynaptic GABAA receptors emerges as an essential factor that tunes neuronal network excitability in vitro and shapes behavioral responses in vivo. To address the role of neuromodulatory transmitter systems on this type of inhibition, we employed pa...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0984-1
更新日期:2018-11-01 00:00:00
abstract::OMI/HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer's disease (AD) are available, but none on its relationship with the cholinergi...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1383-3
更新日期:2019-07-01 00:00:00
abstract::There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons, orchestrate various neuromodula...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-01961-y
更新日期:2020-10-01 00:00:00