Tau is a protein that is highly enriched in neurons and was originally defined by its ability to bind and stabilize microtubules. However, it is now becoming evident that the functions of tau extend beyond its ability to modulate microtubule dynamics. Tau plays a role in mediating axonal transport, synaptic structure and function, and neuronal signaling pathways. Although tau plays important physiological roles in neurons, its involvement in neurodegenerative diseases, and most prominently in the pathogenesis of Alzheimer disease (AD), has directed the majority of tau studies. However, a thorough knowledge of the physiological functions of tau and its posttranslational modifications under normal conditions are necessary to provide the foundation for understanding its role in pathological settings. In this review, we will focus on human tau, summarizing tau structure and organization, as well as its posttranslational modifications associated with physiological processes. We will highlight possible mechanisms involved in mediating the turnover of tau and finally discuss newly elucidated tau functions in a physiological context.

Truncated Tau Affects Mitochondrial Transport and reduction of ATP production available for the process of movement of these organelles. These observations are novel and represent a set of exciting findings whereby tau pathology could affect mitochondrial distribution in neurons, an event that may contribute to synaptic failure observed in AD.

Adolescence is a period of multiple changes where social behaviors influence interpersonal-relations. Adolescents live new experiences, including alcohol consumption which has become an increasing health problem. The age of onset for consumption has declined in the last decades, and additionally, the adolescents now uptake greater amounts of alcohol per occasion. Alcohol consumption is a risk factor for accidents, mental illnesses or other pathologies, as well as for the appearance of addictions, including alcoholism. An interesting topic to study is the damage that alcohol induces on the central nervous system (CNS) in the young population. The brain undergoes substantial modifications during adolescence, making brain cells more vulnerable to the ethanol toxicity. Over the last years, the brain mitochondria have emerged as a cell organelle which is particularly susceptible to alcohol. Mitochondria suffer severe alterations which can be exacerbated if the amount of alcohol or the exposure time is increased. In this review, we focus on the changes that the adolescent brain undergoes after drinking, placing particular emphasis on mitochondrial damage and their consequences against brain function. Finally, we propose the mitochondria as an important mediator in alcohol toxicity and a potential therapeutic target to reduce or treat brain conditions associated with excessive alcohol consumption.

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Ethanol is a licit drug consumed by a large part of the population, from adolescence to adulthood. High ethanol consumption is a public health problem due to its addictiveness and the risk it produces of developing other diseases, including cardiovascular, hepatic, and mental pathologies. Different patterns of ethanol consumption and its toxic effects in the brain have been reported. Current studies suggest to mitochondria, one of the principal mediators for ethanol neurotoxicity. In this chapter, we will review the effects of ethanol on neurons in different scenarios of ethanol consumption and its relation with mitochondrial function. Finally, we will propose a mechanism of ethanol toxicity in which the mitochondria are the main mediator and in which the mitochondrial alterations correlate with the severity of ethanol consumption. Thus, improving mitochondrial health of brain cells could be considered as a potential therapeutic target to treat ethanol-associated disorders.Excessive ethanol use results in brain intoxication, leading to motor and behavior alterations, and eventually to death as a consequence of the depressive effects on the central nervous system (CNS) [6]. These effects result in simultaneous alterations in neuronal circuits including the prefrontal cortex, which controls behavior [7]; the cerebellum, which regulates movement and coordination [8]; the frontal lobe, which controls emotions [9]; the reticular activating system, which determines the sleep-wake cycle [10]; the hippocampus, which mediates learning and memory [8]; and the medulla, which controls vital functions [6]. Ethanol intoxication induces cellular damage and neuronal death [11]. The precise mechanism participating in ethanol toxicity in the brain is unknown. However, at the cellular level, ethanol impairs the neurotransmitters signaling [12]. Also, ethanol promotes reactive oxygen species (ROS) production [13] and activates inflammatory processes [14]. Altogether these events could be responsible for ethanol-induced damage in the brain.Mitochondria are dynamic organelles, which regulate the production of ATP, redox balance, and calcium homeostasis in the neuron [15]. Interestingly, many effectors described in ethanol toxicity are directly or indirectly related to mitochondria. Mitochondria are the main source of ROS in the brain, and they are mainly affected by the oxidative damage induced by ethanol intoxication [16]. Likewise, dysfunctional mitochondria play a role in inducing proinflammatory events [17]. Finally, during synaptic process, ATP production and calcium buffering capacity produced by mitochondria are critical [18,19]; therefore, mitochondrial injury may have severe consequences on neuronal communication.In fact, evidence suggests that ethanol produces catastrophic changes in the mitochondria of organs such as liver [20] and heart [21], and over the last decade, many studies have reported the toxicity of ethanol to the brain's mitochondria [22,23]. Briefly, ethanol increases ROS production [23], alters mitochondrial ...