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些細(xì)胞骨架成分的改變可增加癌細(xì)胞的運(yùn)動(dòng)能力。微管微絲可作為腫瘤化療藥物的靶位,長(zhǎng)春花堿、秋水仙素和細(xì)胞松弛素等及其衍生物作為有效的化療藥物可抑制細(xì)胞增殖,誘導(dǎo)細(xì)胞凋亡。另外,中間絲的不同類(lèi)型嚴(yán)格地分布于不同類(lèi)型的細(xì)胞中,可根據(jù)中間絲的種類(lèi)區(qū)分上皮細(xì)胞、肌肉細(xì)胞、間質(zhì)細(xì)胞、膠質(zhì)細(xì)胞和神經(jīng)細(xì)胞,具有與其來(lái)源組織相關(guān)的特異抗原性,在轉(zhuǎn)化細(xì)胞內(nèi)又無(wú)變化,因此可作為細(xì)胞類(lèi)型區(qū)分的特征性標(biāo)志之一。絕大多數(shù)腫瘤細(xì)胞通常繼續(xù)表達(dá)其來(lái)源細(xì)胞的特征性中間絲類(lèi)型,即便在轉(zhuǎn)移后,仍表達(dá)其原發(fā)腫瘤的中間絲類(lèi)型。因此可用于正確區(qū)分腫瘤細(xì)胞的類(lèi)型及其來(lái)源,對(duì)腫瘤診斷起決定性作用。 ? 許多神經(jīng)性疾病與骨架蛋白的異常表達(dá)有關(guān),早老性癡呆(患者的神經(jīng)元中可見(jiàn)到大量損傷的神經(jīng)元纖維,神經(jīng)元中微管蛋白的數(shù)量并無(wú)異常,但微管聚集缺陷,并存在 tau蛋白的積累。 ? 神經(jīng)元纖維的異常表達(dá)與異常修飾導(dǎo)致某些神經(jīng)系統(tǒng)疾病,如肌萎縮性側(cè)脊髓索硬化癥 ,幼稚型脊柱肌肉萎縮癥 ,神經(jīng)元纖維在運(yùn)動(dòng)神經(jīng)元胞體和軸突近端的堆積是許多神經(jīng)元退化型疾病的早期癥狀,使骨骼肌失去神經(jīng)支配而萎縮,造成癱瘓,接著運(yùn)動(dòng)神經(jīng)元喪失,最終導(dǎo)致死亡。 ? NFH的異常磷酸化也會(huì)導(dǎo)致疾病發(fā)生。在早老性癡呆的神經(jīng)元纖維纏結(jié)和帕金森氏綜和征的 Lewy bodies中都有高度磷酸化的NFH存在。 ? ? 一些遺傳性疾病的患者常有細(xì)胞骨架的異常或細(xì)胞骨架蛋白基因的突變。如角蛋白 14( CK14)基因突變導(dǎo)致人類(lèi)遺傳性皮膚病單純性大泡性表皮松懈癥( epidermolysis bullosa simplex, EBS)。 WiskottAldrich綜合征( WiskottAldrich syndrome, WAS)是 X連鎖隱性遺傳的免疫缺陷疾病,臨床表現(xiàn)有血小板減少、濕疹、反復(fù)感染,并發(fā)不同程度的細(xì)胞免疫和體液免疫缺乏。研究表明, WAS患者的 T淋巴細(xì)胞的微絲異常,微絨毛數(shù)量減少,血小板和淋巴細(xì)胞變小。 ? (2) 突起 ? 分樹(shù)突與軸突 ? ① 樹(shù)突 dendrite ? 一個(gè)或多個(gè),粗短且有分支,結(jié)構(gòu)類(lèi)似細(xì)胞質(zhì)。 ? 功能:接受刺激,傳向胞體。 ? ? ② 軸突 axon ? 只有一條,細(xì)而長(zhǎng),內(nèi)無(wú)尼氏體。 ? ※ 軸丘 axon hillock :無(wú)尼氏體。 ? 功能:傳導(dǎo)興奮沖動(dòng),傳離胞體。 ? Cell body (soma。 perikaryon) ? Axon : only one (branches are collaterals。 terminals are end feet) ? Dendrites : much shorter。 one or more than one。 branch extensively into dendritic trees Structure of Neurons Axon Hillock (Axonal end feet) ? Cell Body (Soma): Life Support – Protein Synthesis – Single Nucleus, RER (Nissl Bodies) ? Axon: Longest process transmits messages away from cell body ? Dendrites: Multiple processes off cell body – receive messages Neurons Structure amp。 Function Neurons are similar to other cells in the body in some ways such as: 1. Neurons are surrounded by a membrane. 2. Neurons have a nucleus that contains genes. 3. Neurons contain : What are inside of a neuron? Nucleus Nucleolus Microfilaments/Neurotubules Endoplasmic Reticulum (ER) Mitochondria Golgi Apparatus Nissl Bodies Others ? Dendrites : – dendrite tree ? Axon : – axon hillock (axon origination) – axonal transport system – initial segment (first myelin sheath) ? action potential generation – myelin sheath Axon and Dendrites Axons Dendrites Take information away from the cell body Take information to the cell body Smooth surface Rough surface (dendritic spines) Generally only 1 axon per cell Usually many dendrites per cell No ribosome Have ribosomes Can have myelin No myelin insulation Branch further from the cell body Branch near the cell body Differences between Axons and Dendrites Neuron Classification by Shape ?Multipolar: “multi” many processes –Majority: Single axon, many dendrites (motor neuron and interneuron) ?Bipolar: “bi” 2 processes –Found in some sensory ans (retina, taste, smell, inner ear neuron) ?Unipolar (pseudounipolar): “uni ” 1 process (with branches) –Sensory afferent neurons (dorsal root ganglia) ? 神經(jīng)元的分類(lèi) ? : ? ? ? multipolar neuron ? ? ? bipolar neuron ? ? ? pseudounipolar neuron ? ? : ? sensory neuron :傳入神經(jīng)元 ? motor neuron : 傳出神經(jīng)元 ? inter neuron : 聯(lián)絡(luò)神經(jīng)元 ? : ? ? ? ? : ? I 型神經(jīng)元 ? II 型神經(jīng)元 Classification of Neurons by Morphology Classification of Neurons by Axon Length 1. Golgi type I Neurons ? Long axons (longest from the cortex to the tip of spinal cord, 5070 cm) 2. Golgi type II Neurons ? Short axons (shortest axons terminate only a few micron from cell body, interneurons) 3. Amacrine Neurons ? An unusual cell type, lack axons – Sensory neuron ?from receptor to CNS。 receive stimuli and transmit afferent impulses to CNS – Interneurons ?municating between neurons。 form circuits in the CNS – Motor neuron ?from CNS to effector cells。 deliver efferent impulses out through the PNS to the effectors to carry out the actions directed by the CNS Functional Classification of Neuron ? EXCITABLE Membrane: Able to regulate the movement of ions (charges) across and along membrane SIGNAL TRANSDUCTION ? DO NOT Replicate: Damaged cells cannot be replaced! Important Features of Neurons Action Potential Four Functional Regions of Model Neurons 突觸 ? 定義:突觸是 ( synapse) 神經(jīng)元與神經(jīng)元之間,或神經(jīng)元與非神經(jīng)細(xì)胞之間的一種特化結(jié)構(gòu)。 ? Impulse transmission : – electrical – chemical ? Morphology : – axodendritic – axonsomatic – axoaxonic – dendrodendritic Classification of Synapses ? 分類(lèi):化學(xué)性突觸、電突觸 ? ? 結(jié)構(gòu): ? 電突觸 :縫隙連接 ? ? 突觸小泡 :神經(jīng)遞質(zhì)神經(jīng)調(diào)質(zhì) ? 突觸前成分 ? 突觸前膜 ? 突觸間隙 ? ? 突觸后成分 :突觸后膜、受體、酶 化學(xué)性突觸超微結(jié)構(gòu)模式圖 化學(xué)性突觸超微結(jié)構(gòu) synapse 4 Vesicles release Neurotransmitters ? Chemical synapse : – presynaptic knob (presynaptic ponent) ? synaptic vesicles – synaptic cleft – postsynaptic membrane (postsynaptic ponent) ? Electrical synapse : – gap junctions Synapse Structures Types of synapse Distance Cytoplasmic continuity Ultrastructural ponent Agent of