| 1. |
- Lema Tomé, Carla, et al.
(författare)
-
Inflammation and α-Synuclein's Prion-like Behavior in Parkinson's Disease-Is There a Link?
- 2013
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 47:2, s. 561-574
-
Forskningsöversikt (refereegranskat)abstract
- Parkinson's disease patients exhibit progressive spreading of aggregated α-synuclein in the nervous system. This slow process follows a specific pattern in an inflamed tissue environment. Recent research suggests that prion-like mechanisms contribute to the propagation of α-synuclein pathology. Little is known about factors that might affect the prion-like behavior of misfolded α-synuclein. In this review, we suggest that neuroinflammation plays an important role. We discuss causes of inflammation in the olfactory bulb and gastrointestinal tract and how this may promote the initial misfolding and aggregation of α-synuclein, which might set in motion events that lead to Parkinson's disease neuropathology. We propose that neuroinflammation promotes the prion-like behavior of α-synuclein and that novel anti-inflammatory therapies targeting this mechanism could slow disease progression.
|
|
| 2. |
- Schiöth, Helgi B., et al.
(författare)
-
Brain Insulin Signaling and Alzheimer's Disease : Current Evidence and Future Directions
- 2012
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 46:1, s. 4-10
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.
|
|
| 3. |
- Sharma, Aruna, et al.
(författare)
-
Size- and Age-Dependent Neurotoxicity of Engineered Metal Nanoparticles in Rats
- 2013
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 48:2, s. 386-396
-
Tidskriftsartikel (refereegranskat)abstract
- Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50-60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood-brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier.
|
|
| 4. |
- Sharma, Hari S., et al.
(författare)
-
Exacerbation of Brain Pathology After Partial Restraint in Hypertensive Rats Following SiO2 Nanoparticles Exposure at High Ambient Temperature
- 2013
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 48:2, s. 368-379
-
Forskningsöversikt (refereegranskat)abstract
- This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 A degrees C) or at 33 A degrees C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine (([131]-)Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 A degrees C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.
|
|
| 5. |
- Yang, Xiaoguang, et al.
(författare)
-
Cellular Membrane Fluidity in Amyloid Precursor Protein Processing
- 2014
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 50:1, s. 119-129
-
Tidskriftsartikel (refereegranskat)abstract
- The senile plaque is a pathologic hallmark of Alzheimer's disease (AD). Amyloid-beta peptide (A beta), the main constituent of senile plaques, is neurotoxic especially in its oligomeric form. A beta is derived from the sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases in the amyloidogenic pathway. Alternatively, APP can be cleaved by alpha-secretases within the A beta domain to produce neurotrophic and neuroprotective alpha-secretase-cleaved soluble APP (sAPP alpha) in the nonamyloidogenic pathway. Since APP and alpha-, beta-, and gamma-secretases are membrane proteins, APP processing should be highly dependent on the membrane composition and the biophysical properties of cellular membrane. In this review, we discuss the role of the biophysical properties of cellular membrane in APP processing, especially the effects of phospholipases A(2) (PLA(2)s), fatty acids, cholesterol, and A beta on membrane fluidity in relation to their effects on APP processing.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Levi-Montalcini, R, et al.
(författare)
-
Rita's 102!!
- 2011
-
Ingår i: Molecular neurobiology. - 1559-1182. ; 43:2, s. 77-79
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
|
|
