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Neurons of the locus coeruleus of a case of Parkinson's disease associated with dementia aged 62 years (N DPD). The loss of dendritic spines and the decrease of spine density is obvious: neuron of the locus coeruleus of a patient aged 65 years who suffered from Parkinson's disease, without dementia (N PD) (Rapid Golgi staining, × 2,000).
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Electron microscopy has enlarged the visual horizons of the morphological alterations in Alzheimer's disease (AD). Study of the mitochondria and Golgi apparatus in early cases of AD revealed the principal role that these important organelles play in the drama of pathogenic dialog of AD, substantially affecting energy production and supply, and prot...
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... In addition, oxidative stress, due to mitochondrial dysfunction, plays a principal role, as causative factor, in the neurodegeneration [67] and in Alzheimer's disease particularly [68,69], and it is considered as been among the potential risk factors for the neurometabolic and neoplastic diseases, as well as obesity [70]. ...
Mitochondria (from Greek mito, μίτος: thread, and chondrion, χόνδριον: thick granule) are principal cell organelles, which participate in a wide spectrum of essential cellular functions, being the main energy providers for living eukaryotic cells, especially for neurons and glia, which are characterized by high metabolic activity and energy consumption.
Thus, it is expectable that mitochondrial dysfunction, having pleotropic effect on the cell, may play a crucial role in a substantial number of serious neurological disorders including Alzheimer’s disease (AD) [1,2], Parkinson’s disease (PD) [3] Huntington’s disease [4,5], Amyotrophic lateral sclerosis (ALS) [6], Multiple Sclerosis (MS) [7, 8] as well as some of the major psychiatric diseases [9], given that both, neurons and glia are particularly sensitive and vulnerable to energy decline [10].
Mitochondria hypothesis of those devastating diseases advocates reasonably in favor of the important role that mitochondrial dysfunction may play in the early stages of neurodegeneration by inducing energy deficiency and oxidative stress [11].
However, the majority of the mitochondrial diseases, being maternally inherited, which are designated as mitochondrial encephalomyopathies [12], are closely connected either with the impairment of nucleus-to-mitochondria signaling or with mutations in mtDNA or nuclear genome that affect seriously the mitochondrial respiratory function even from the initial steps of the life [13], inducing defective oxidative phosphorylation (OXPHOS).
The proteins presenilin-1/2 play a key role in the interactions between mitochondria and the endoplasmic reticulum at synaptic contacts of central neurons. Several novel observations suggest that mutations in presenilin-1 lead to an abnormal energy state, an early sign of neurodegeneration and Alzheimer’s disease. Recent studies suggest that in the postsynaptic region, calcium stores are widely represented in the spine apparatus, which is located in a strategically important compartment - the neck of mature mushroom-shaped dendritic spines. Moreover, in the dendritic shaft area, at the base of the spines, one finds oblong mitochondrial clusters supplying the postsynaptic area and the local protein synthesis with ATP. Calcium signals, generated by the postsynaptic membranes, affect both calcium release from local stores through ryanodine channels and the uptake based on store-operated calcium entry. The entire complex of nanoscale signaling most likely determines the production of ATP. Violation of the functional relationship between mitochondria and reticular calcium depots can lead to disruption of signaling pathways that stimulate ATP production at the stages of increased activity of individual synapses. In this chapter, we will present the signaling mechanisms of interaction between mitochondria, spine clusters, and calcium nano-stores in postsynaptic area.
