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Figure 1. Genetic architecture of ASD. Genetic contributions to ASD can also be caused by direct or indirect effects on genes and
proteins by environmental influences. ASD: autism spectrum disorder

including schizophrenia and autism are associated with synapse development and abnormal dendritic spine
[32]
formation . Pathological events affecting the temporal lobe, especially the amygdala and the hippocampus,
[33]
are thought to be related to the development of symptoms similar to autism . Bilateral disorders in the
cerebellum, thalamus, hippocampus, and amygdala regions were detected in autism .
[34]
AUTOPHAGY MECHANISM
Autophagy is a type of cell death mechanism that functions as an intracellular quality control system to
[35]
maintain homeostasis by removing damaged proteins . Autophagy is also a cell-protective mechanism
that allows cell survival in low nutrient conditions and controls cell quality under stress conditions, often
[36]
through degradation of aging and damaged proteins and organelles . Autophagy is carried out by at least
three different mechanisms, microautophagy, macroautophagy, and chaperone dependent autophagy.
Macroautophagy occurs at the basic level in most cells, playing an important role in the breakdown of
damaged organelles and proteins. Microautophagy is the event of lysis of the cytoplasm directly by the
lysosome and digestion of the cytoplasm content within the lysosome with the lysosome membrane
collapsing inward. And, chaperone-mediated autophagy selectively transfers proteins with KFERQ motifs
[37]
to the lysosome membrane .

Autophagy is induced by starvation, oxygen deficiency, and various stress conditions. In these cases,
the target of rapamycin (TOR) complex is activated for the initiation of autophagy. The TOR complex is
the key protein that controls the cell’s energy metabolism, protein synthesis, and cell growth. It was first
identified as the target molecule of rapamycin, an immunosuppressive agent developed for use against
yeast in fungi. The isoform in mammals is known as mTOR, and suppression of this protein or silencing of
the mTOR gene through various gene modifications provides stimulation of autophagy . It is also known
[38]
that the dysregulation of the autophagy mechanism is associated with human diseases such as cancer and
[39]
neurodegeneration. Therefore, autophagy has attracted considerable interest in the biological sciences .
Several autophagic proteins control this pathway. BECN1 is a principal player in autophagy, triggering